Cortisol And Post-COVID Research

Last updated: October 4, 2026 - Reviewed by Verdant Wellness Editorial Team

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By Gabriela Mitchell, Registered Dietitian (Linkedin)

Last Updated September 2026  ·  30 min read

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Table of Contents

• What Is Cortisol And Why Does It Matter After COVID-19?
• The HPA Axis: Long COVID's Overlooked Control System
• What Recent Studies Actually Found About Post-COVID Cortisol
• Why Some Studies Find Low Cortisol While Others Find No Difference
• Morning Cortisol vs. Random Cortisol: Does Timing Change Everything?
• Salivary vs. Blood Cortisol Tests in Long COVID Research
• Cortisol, Fatigue, and Brain Fog: Is There a Connection?
• Post-COVID Adrenal Function: Is the Adrenal Gland the Problem?
• Can Cortisol Levels Diagnose Long COVID?
• Do Corticosteroids Help If Cortisol Is Abnormal?
• What This All Means For Patients Right Now
• Frequently Asked Questions

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What Is Cortisol And Why Does It Matter After COVID-19?

Cortisol is a steroid hormone produced by the adrenal glands, two small glands that sit just above your kidneys. In healthy individuals, cortisol follows a predictable 24-hour pattern: levels peak sharply in the early morning, typically within 30 to 45 minutes of waking, then gradually decline through the day and bottom out around midnight. This rhythm governs a remarkable number of body functions — energy metabolism, immune regulation, blood pressure, inflammatory response, sleep quality, mood, and cognitive performance.

When you experience physical or psychological stress, the brain triggers a cascade through a network called the hypothalamic-pituitary-adrenal axis, commonly abbreviated as the HPA axis. The hypothalamus releases corticotropin-releasing hormone (CRH), which tells the pituitary to release adrenocorticotropic hormone (ACTH), which in turn signals the adrenal glands to produce cortisol. This elegant feedback loop normally self-regulates — when cortisol reaches a threshold, it signals the hypothalamus and pituitary to stand down.

COVID-19, however, does not interact with the human body in a normal way. During acute infection, SARS-CoV-2 triggers a systemic inflammatory response significant enough to directly stimulate the adrenal glands, often resulting in elevated cortisol during the acute phase. A 2024 review on endocrine dysregulation in COVID-19 confirmed this pattern, noting that systemic inflammation during acute infection routinely pushed cortisol upward. The critical question for long COVID science is what happens after the acute phase resolves — because for millions of people, something clearly goes wrong in the recovery period, and the post COVID cortisol picture looks far messier than anyone initially expected.

Understanding cortisol long COVID dynamics matters because cortisol touches nearly every system implicated in long COVID symptomatology: the immune system, the autonomic nervous system, sleep architecture, metabolic regulation, and the brain's capacity to manage energy and attention. If the HPA axis is dysregulated after COVID-19, the downstream effects would not produce one or two isolated symptoms. They would produce exactly the kind of diffuse, multi-system dysfunction that defines long COVID.

The HPA Axis: Long COVID's Overlooked Control System

The HPA long COVID connection has gained substantial research attention since 2022, but it remains underappreciated in clinical settings. Most discussions of long COVID pathophysiology focus on viral persistence, microclots, immune dysregulation, and mitochondrial dysfunction. The neuroendocrine angle — specifically, what happens to the brain-adrenal communication system after a COVID-19 infection — receives comparatively little clinical attention, even though the evidence increasingly suggests it matters.

The long COVID HPA axis story begins in the brain, not the adrenal glands. The hypothalamus and pituitary gland can be directly affected by SARS-CoV-2 through several mechanisms: neuroinvasion via the olfactory route, systemic inflammation crossing the blood-brain barrier, autoimmune attack on neuroendocrine tissue, and chronic neuroinflammation persisting well after the virus has been cleared. Any of these mechanisms could disrupt the upstream regulation of cortisol production without necessarily damaging the adrenal glands themselves.

This distinction — central dysregulation versus adrenal damage — is critical and often overlooked. A patient with a normally functioning adrenal gland can still have profoundly abnormal cortisol patterns if the hypothalamus or pituitary is not sending the right signals. This is why some researchers have shifted focus from asking whether the adrenal gland is damaged (the answer appears to be largely no, in most patients) toward asking whether the HPA axis is sending and receiving signals correctly across the full 24-hour cycle.

HPA COVID research has also been complicated by the enormous heterogeneity within long COVID itself. Long COVID is not a single disease. It encompasses patients with predominantly fatigue-dominant illness, patients with dysautonomia, patients with cognitive impairment, patients with post-exertional malaise consistent with ME/CFS criteria, and patients with predominantly respiratory or cardiovascular symptoms. Each of these subgroups may interact with HPA axis function differently, which could explain why population-level studies frequently find inconclusive average results.

The long COVID stress hormones question also extends beyond cortisol. Adrenaline (epinephrine), noradrenaline (norepinephrine), aldosterone, and DHEA-S are all regulated through pathways that overlap with the HPA axis or interact with it. Some long COVID researchers have documented elevated catecholamines consistent with sympathetic nervous system overdrive, which would interact with HPA axis function in complex ways. But cortisol remains the most studied and arguably most clinically accessible marker in this space.

What Recent Studies Actually Found About Post-COVID Cortisol

The research landscape on cortisol and post-COVID research from 2024 through 2026 is genuinely complex — and honest science communication requires presenting what studies actually found, including their contradictions, rather than forcing a clean narrative.

The 2026 Salivary Cortisol Study

The most methodologically detailed recent investigation is a 2026 study examining salivary cortisol rhythms in long COVID patients compared to asymptomatic post-COVID individuals and healthy controls. This study found a flattened circadian salivary cortisol rhythm in long COVID patients. Specifically, long COVID patients showed reduced morning cortisol and elevated evening cortisol compared to both comparison groups. Additionally, ACTH levels were higher in the long COVID group than in asymptomatic post-COVID individuals and healthy controls.

This pattern — high ACTH combined with a blunted morning cortisol rise — suggests that the pituitary is working overtime trying to stimulate cortisol production, but the resulting cortisol output is not following the expected circadian pattern. The elevated evening cortisol is, if anything, more clinically significant than the reduced morning level, because high evening cortisol disrupts sleep architecture, maintains inflammatory signaling at times when the body should be in restoration mode, and disrupts the metabolic processes that depend on cortisol's daily low point.

This study's findings are consistent with central HPA dysregulation rather than adrenal insufficiency. The adrenal glands appear to still be producing cortisol when stimulated — but the timing and amplitude of production is disrupted.

The 2024 medRxiv Preprint

A 2024 cross-sectional preprint study examined 144 people with long COVID and 56 fully recovered controls, measuring morning plasma cortisol. The headline finding was deliberately unsensational: overall morning cortisol was 8.9 µg/dL in the long COVID group versus 8.8 µg/dL in controls, with a p-value of 0.97. That is about as non-significant as a result can be.

However, the story did not end there. When the researchers restricted their analysis to the 8–9 AM time window specifically, a subset of long COVID patients meeting criteria for ME/CFS showed a lower median cortisol of 8.2 µg/dL compared to 8.8 µg/dL in controls. This difference, while still modest, suggests that the precise timing of cortisol measurement matters enormously. A difference in cortisol rhythm that peaks and troughs even 30 to 60 minutes off-schedule from healthy controls would be systematically missed by studies using broad collection windows.

This study is important because it illustrates how population-level null results can obscure clinically meaningful patterns in specific subgroups — particularly the ME/CFS-overlap group that many researchers now consider the most biologically distinct long COVID phenotype.

The 2025 Review on Low Cortisol Controversy

A 2025 commentary and review took a deliberately measured stance on low cortisol in long COVID, arguing that the finding is controversial and that most patients do not have frank adrenal insufficiency. Among the patients assessed in this review, 62.8% had cortisol in the normal range, 36.0% had elevated cortisol, and only 1.2% had low cortisol. This distribution is striking because it suggests that if anything, elevated cortisol may be more common than low cortisol in long COVID populations — the opposite of what earlier widely-cited research suggested.

The authors emphasized circadian timing and the need for serial measurements rather than single-point assessments. They argued that the apparent contradiction between studies finding low cortisol and studies finding elevated or normal cortisol could largely be resolved by considering when cortisol was measured, how it was measured (saliva versus blood), and which long COVID subgroup was studied.

The 2025 CROI Poster Data

Conference poster data presented at CROI 2025 reported that adrenal dysfunction was not a major mechanism in long COVID and that cortisol levels were not significantly different between people with and without long COVID. This finding is consistent with the 2024 preprint's overall null result and supports the view that gross adrenal insufficiency is not driving long COVID for most patients — though it does not rule out subtler circadian dysregulation or HPA axis signaling problems.

The 2026 Post-COVID Status Study

A separate 2026 study examining people with prior COVID-19 nearly two years after infection found higher salivary cortisol in the post-COVID group compared to controls who had never been infected. This finding — elevated rather than diminished cortisol — aligns with the elevated evening cortisol finding from the salivary circadian study and suggests that persistent HPA axis activation may be a feature of post-COVID biology even at long time intervals from infection. This is less consistent with adrenal exhaustion and more consistent with a chronically activated, dysregulated stress response system.

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Why Some Studies Find Low Cortisol While Others Find No Difference

This is arguably the most important methodological question in cortisol and post-COVID research, and understanding it requires appreciating several sources of systematic variation across studies.

1. Measurement Timing Is Not Standardized

Cortisol is not a stable biomarker. It changes by 50% or more within a 30-minute window in the early morning. A study collecting blood between 8:00 and 10:00 AM may have participants measured across a cortisol range of 6–18 µg/dL, depending on exactly when they arrived at the clinic. If long COVID patients have a delayed or blunted cortisol awakening response, they would appear to have lower cortisol than controls when measured at 8:15 AM but similar or higher cortisol when measured at 9:45 AM. This timing artifact alone could produce apparently contradictory results across studies.

2. Salivary vs. Blood Cortisol Capture Different Things

Salivary cortisol measures free, biologically active cortisol. Blood cortisol measurements typically capture total cortisol, which includes cortisol bound to cortisol-binding globulin and albumin. Inflammation — which is chronically present in many long COVID patients — can alter cortisol-binding globulin levels, potentially making blood cortisol appear normal even when free cortisol is abnormal. Studies using salivary cortisol may therefore be more sensitive to the kind of HPA axis dysregulation present in long COVID.

3. Long COVID Is Not One Disease

Studies that group all long COVID patients together will consistently produce noisier results than studies that stratify by phenotype. The ME/CFS-overlap subgroup appears to have the most consistent cortisol findings, while patients with primarily respiratory or cardiovascular long COVID may not show the same HPA axis alterations. Pooling these populations dilutes any signal.

4. Single-Point Measurements Miss Dynamic Dysfunction

A single blood draw or even a single salivary sample cannot capture circadian rhythm disruption. The 2026 study's finding of a flattened rhythm — lower morning AND higher evening — would be missed entirely by a single morning measurement. To detect circadian flattening, you need serial measurements across the day, ideally using standardized salivary collection protocols at waking, 30 minutes post-waking, afternoon, and evening.

5. Study Population Differences

Whether a study recruits patients from post-COVID clinics, primary care registries, online surveys, or hospital follow-up programs will dramatically affect the disease severity profile of its sample. More severely affected patients — those most likely to show HPA axis changes — may be systematically underrepresented in studies that require in-person attendance if fatigue and post-exertional malaise prevent clinic attendance.

6. Time Since Infection Varies

The 2026 post-COVID status study measuring elevated cortisol nearly two years after infection suggests that HPA axis dynamics may evolve over time. Early post-COVID studies may have captured one phase of HPA response, while later studies capture another.

Morning Cortisol vs. Random Cortisol: Does Timing Change Everything?

The short answer is yes, and the evidence strongly supports this conclusion. The cortisol long COVID literature is increasingly converging on the view that when you measure cortisol is at least as important as how you measure it.

The cortisol awakening response (CAR) — the sharp rise in cortisol in the first 30 to 45 minutes after waking — is one of the most studied markers of HPA axis function. It is regulated by distinct neural pathways compared to the diurnal cortisol slope, and it is thought to reflect anticipatory physiological preparation for the demands of the day. In populations with burnout, chronic fatigue, and various stress-related conditions, the CAR is frequently attenuated.

In long COVID, the 2026 salivary study's finding of reduced morning cortisol alongside elevated ACTH is particularly significant because it suggests that the normal CAR amplification may be blunted — not because ACTH signaling has stopped, but because the rhythmic response to ACTH has been disrupted. The pituitary is sending the signal; the adrenal response is misfiring in its timing.

The 2024 preprint's finding of lower 8–9 AM cortisol specifically in the ME/CFS-overlap subgroup supports this interpretation. If the CAR is blunted, the cortisol level at 8–9 AM would appear lower than controls, but levels at 9–10 AM or later might converge, explaining why studies using broad morning windows find no overall difference.

Practically, this means:

• A random morning blood cortisol is unlikely to detect the HPA axis abnormalities present in long COVID with meaningful sensitivity
• Standardized salivary CAR protocols (waking sample, +30 minutes, +60 minutes) are more appropriate for research and potentially for clinical assessment
• The diurnal slope — the rate at which cortisol falls across the day — provides additional information that a single morning measurement cannot

The 2025 review's emphasis on serial measurements and circadian timing was not merely a methodological footnote. It reflects a fundamental truth about HPA axis assessment: the axis is a dynamic system, and dynamic systems cannot be characterized by a single static measurement.

Salivary vs. Blood Cortisol Tests in Long COVID Research

The choice of measurement matrix significantly affects what cortisol post viral research can detect and interpret.

Blood (plasma or serum) cortisol measures total cortisol, including protein-bound forms. It requires venipuncture, which itself can elevate cortisol through the stress of the procedure. Standardization is difficult in clinical settings because of the narrow measurement windows required for meaningful circadian assessment, and chronic inflammation in long COVID patients can alter cortisol-binding globulin, potentially masking free cortisol changes.

Salivary cortisol reflects only the free, biologically active fraction — the fraction that actually enters cells and exerts physiological effects. It can be collected at home under standardized conditions, enabling multiple time-point sampling without the confounders introduced by clinic visits. This is why the 2026 salivary study was able to characterize the full circadian profile of long COVID patients, yielding the flattened rhythm finding that blood-draw studies have missed.

Salivary collection considerations are not trivial, however. Food, drink, oral inflammation, and even vigorous exercise before sampling can affect results. Standardized protocols typically require fasting from food for at least 30 minutes before sampling, avoiding certain foods and medications, and collecting during specific time windows. Studies that fail to standardize these factors will produce noisy results.

Urine cortisol — specifically 24-hour urinary free cortisol — captures total daily cortisol output and is relatively insensitive to the timing issues that affect single-point blood or saliva measurements. It would miss circadian pattern disruption (because it averages across the day) but would detect overall hyper- or hypocortisolism. The fact that most urine cortisol studies in long COVID populations have not found frank hypocortisolism is consistent with the current picture: total cortisol output may be relatively normal even when the circadian distribution is abnormal.

For long COVID HPA axis research moving forward, the 2026 salivary circadian study methodology — measuring salivary cortisol at multiple standardized time points alongside ACTH — represents the current gold standard approach. The addition of ACTH measurement is crucial because it allows researchers to determine whether any cortisol abnormality reflects a primary adrenal problem (low cortisol with low ACTH, or adrenal hyperresponsiveness) versus a central HPA axis problem (elevated ACTH with disrupted cortisol rhythm, as found in the 2026 study).

Cortisol, Fatigue, and Brain Fog: Is There a Connection?

Long COVID fatigue cortisol is a particularly active area of inquiry because fatigue is the single most prevalent and debilitating symptom in long COVID, and because cortisol's role in energy mobilization and alertness makes it a biologically plausible contributor.

Normal morning cortisol serves several functions relevant to fatigue and cognitive function:

• Energy mobilization: cortisol promotes gluconeogenesis, ensuring adequate blood glucose for brain and muscle function upon waking
• Anti-inflammatory action: morning cortisol suppresses nocturnal immune activation, helping transition from the immunologically active nighttime period to daytime activity
• Alerting effect: cortisol interacts with dopamine and noradrenaline systems to promote wakefulness, attention, and motivational drive
• Circadian synchronization: morning cortisol helps synchronize peripheral clocks throughout the body, contributing to the overall coherence of the circadian system

When morning cortisol is blunted — as suggested by the 2026 salivary study and the 2024 ME/CFS-overlap findings — each of these functions is partially compromised. The result would be difficulty achieving full alertness upon waking, impaired energy mobilization, persistent morning inflammatory signaling, and disrupted circadian coherence — a symptom cluster that maps closely onto what long COVID fatigue patients describe.

The elevated evening cortisol finding is, if anything, more disruptive for functional recovery. High cortisol in the evening impairs sleep onset, reduces slow-wave sleep depth, and maintains inflammatory signaling during the period when tissue repair and immune memory consolidation should be occurring. Patients with this pattern — low morning, high evening — would wake unrefreshed, struggle through the morning, and then experience a secondary activation in the evening that interferes with sleep, producing a self-perpetuating cycle.

Brain fog in long COVID may have additional cortisol-related mechanisms. Cortisol receptors are densely expressed in the hippocampus — the brain region central to memory formation and consolidation. Chronically abnormal cortisol patterns are known to impair hippocampal function, working memory, and executive processing. Whether the cortisol changes seen in long COVID are large enough to drive the brain fog that patients report is not yet established, but the neurobiological plausibility is strong.

Post-exertional malaise (PEM) — the hallmark of ME/CFS overlap in long COVID — may involve its own HPA axis dynamic. Some researchers have proposed that the normal cortisol response to physical exercise is blunted or abnormally timed in patients with PEM, meaning the body cannot mount the appropriate stress hormone response to support physical activity, leading to the characteristic delayed-onset symptom crash. This remains an active research question, but it represents one of the most compelling mechanistic hypotheses for PEM in the long COVID-HPA axis framework.

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Post-COVID Adrenal Function: Is the Adrenal Gland the Problem?

Based on the current research evidence, the answer appears to be: not primarily, in most patients. The post COVID adrenal gland itself does not appear to be the major site of dysfunction for the majority of long COVID patients.

The CROI 2025 poster data specifically reported preserved adrenal function and no significant cortisol differences attributable to adrenal damage. The 2025 review's distribution data — with only 1.2% of assessed patients showing low cortisol — is inconsistent with widespread primary adrenal insufficiency. And the 2026 salivary study's finding of elevated ACTH alongside a disrupted cortisol rhythm points upstream toward the hypothalamus and pituitary rather than toward the adrenal gland as the primary site of pathology.

This is an important distinction clinically. Primary adrenal insufficiency — where the adrenal gland itself is damaged and cannot produce cortisol regardless of stimulation — is a serious, potentially life-threatening condition that requires hormone replacement therapy. The evidence suggests this is not what most long COVID patients have. What they appear to have instead is a more subtle central dysregulation: the HPA axis is receiving or processing signals abnormally, producing a disrupted cortisol rhythm rather than complete adrenal shutdown.

Some cases of COVID-19-associated adrenal insufficiency have been documented in the literature, and these appear to represent a genuine but uncommon complication likely involving adrenal vasculitis, thrombosis, or autoimmune attack. Patients who develop new symptoms consistent with adrenal insufficiency after COVID-19 — profound fatigue, orthostatic hypotension, salt craving, and unexplained weight loss — should be evaluated medically with formal dynamic testing. But this phenotype appears distinct from the broader long COVID population's HPA axis findings.

Cortisol COVID recovery dynamics in the adrenal context may also be influenced by the acute phase. High cortisol during acute COVID-19 infection represents normal adrenal stress response. After recovery, if the adrenal glands have been maximally stimulated for weeks, some degree of relative functional recovery or recalibration would be expected. Whether this recalibration process is impaired in long COVID patients — leaving the HPA axis in an abnormal new setpoint — is a central research question. The evidence from 2025 and 2026 suggests that for some patients, the setpoint is indeed abnormal, but in the direction of circadian disruption rather than wholesale adrenal failure.

It is also worth noting that post COVID adrenal findings need to be interpreted against the baseline risk of other conditions. Autoimmune adrenal insufficiency (Addison's disease) has a known association with various viral infections as precipitating factors. COVID-19 is unlikely to be unique in this respect. Clinicians evaluating post-COVID patients with symptoms suggesting adrenal insufficiency should perform appropriate investigations, but should not assume that abnormal cortisol findings in most long COVID patients represent this diagnosis.

Can Cortisol Levels Diagnose Long COVID?

The honest answer, based on current evidence, is no — at least not in any clinically useful sense as a single diagnostic test. But the more nuanced answer is that cortisol measurements, particularly serial salivary measurements capturing the full circadian profile, may contribute meaningfully to characterizing long COVID biology and identifying specific subgroups.

Consider what the current data actually shows. The 2024 preprint found essentially identical overall morning plasma cortisol between long COVID patients and controls (8.9 versus 8.8 µg/dL, p = 0.97). The 2025 review found that nearly two-thirds of patients assessed had cortisol in the normal range. The CROI 2025 data found no significant cortisol difference. If you were to order a standard morning cortisol blood test on a long COVID patient using these population-level findings as your reference, you would almost certainly get a normal result, and you would learn little.

However, this is a biomarker sensitivity problem, not a pathophysiology problem. The 2026 circadian study's findings of a flattened rhythm with elevated ACTH — findings that would not be captured by a standard morning cortisol test — demonstrate that there is a real biological signal. It is simply a signal that requires the right measurement approach to detect.

What cortisol testing might offer in long COVID:

1. Ruling out adrenal insufficiency: A normal cortisol level in a long COVID patient with severe fatigue effectively rules out primary adrenal insufficiency as the cause, which is clinically useful for guiding treatment decisions
2. Characterizing HPA axis function in research settings: Serial salivary cortisol plus ACTH measurements could help characterize which long COVID patients have HPA axis dysregulation, potentially identifying a subgroup that might respond differently to interventions
3. Tracking recovery: Longitudinal cortisol measurements in individual patients might detect normalization of circadian rhythm as a potential biomarker of physiological recovery
4. Distinguishing long COVID from other conditions: Some conditions in the long COVID differential diagnosis — including primary adrenal insufficiency, Cushing's syndrome, and hypothyroidism — have characteristic cortisol profiles that could be identified or excluded

What cortisol testing cannot currently offer: a single diagnostic test that confirms or excludes long COVID. The overlap between normal and abnormal cortisol in long COVID populations, and the measurement methodology challenges described above, preclude this application currently.

Do Corticosteroids Help If Cortisol Is Abnormal?

This is an area where the research is genuinely limited and where clinical caution is warranted. The long COVID stress hormones research community has not produced high-quality clinical trial evidence supporting corticosteroid treatment for long COVID patients with cortisol abnormalities.

From a theoretical standpoint, if long COVID patients had frank adrenal insufficiency with genuinely low cortisol and high ACTH, cortisol replacement (hydrocortisone) would be indicated — just as it is for any patient with adrenal insufficiency regardless of cause. The 1.2% of patients with low cortisol in the 2025 review might represent this group, and those patients presumably warrant medical evaluation and possible replacement.

But for the majority of long COVID patients whose cortisol is in the normal range or even elevated, and whose pattern appears to represent circadian disruption rather than absolute deficiency, empirical corticosteroid treatment poses risks that would need to be weighed against uncertain benefits:

• Suppression of endogenous cortisol production: exogenous corticosteroids suppress HPA axis activity through negative feedback, potentially worsening the underlying dysregulation rather than correcting it
• Immune suppression: in patients where long COVID may involve viral persistence or ongoing immune activation, corticosteroid immunosuppression could be counterproductive
• Metabolic effects: chronic corticosteroid use carries well-established metabolic risks
• Dependency and withdrawal: HPA axis recovery after exogenous steroid use requires careful tapering

It is worth noting that during acute COVID-19 hospitalization, dexamethasone was found to reduce mortality in patients requiring oxygen support — but this effect appears to be through suppression of the acute cytokine response, not through correcting HPA axis dysregulation, and it is not generalizable to long COVID management.

Current clinical consensus does not support empirical corticosteroid treatment for long COVID patients based on cortisol testing alone, outside of confirmed adrenal insufficiency. Patients interested in this approach should discuss it with an endocrinologist familiar with long COVID, and should not self-treat with over-the-counter cortisol-related supplements without medical guidance.

Non-pharmacological approaches that support healthy cortisol rhythms — consistent sleep-wake timing, morning light exposure, stress management, avoiding late-night stimulants and bright light, and gradual aerobic reconditioning within post-exertional malaise limits — have reasonable theoretical support and no significant risks.

What This All Means For Patients Right Now

If you are living with long COVID and wondering what the cortisol and post-COVID research means for you, here is an honest synthesis.

The biological signal is real. Multiple independent research groups, using different methodologies, in different countries, have found evidence of HPA axis abnormalities in long COVID patients. The 2026 salivary circadian study, with its detailed multi-timepoint methodology and ACTH measurements, provides some of the strongest evidence yet that the cortisol rhythm is genuinely disrupted in a subset of long COVID patients. This is not a minor statistical artifact.

The clinical utility is still limited. Standard cortisol tests available in most clinical settings are unlikely to detect the circadian disruptions that research studies are finding. A normal morning blood cortisol does not mean your HPA axis is functioning normally. This is frustrating, but it is the current reality.

Your adrenal glands are probably not the primary problem. The evidence consistently points toward central HPA axis dysregulation — a signaling problem — rather than adrenal gland damage. This is potentially good news because it implies the system may be capable of recalibration, whereas structural adrenal damage would be harder to reverse.

Circadian hygiene matters more, not less. If the cortisol rhythm is disrupted in long COVID, behaviors that support circadian rhythm — consistent sleep timing, morning light exposure, avoiding bright light after dark, regular meal timing, and managing stress — become especially important. These interventions are safe, accessible, and supported by the broader circadian medicine literature.

Subgroup matters. Long COVID patients with ME/CFS overlap appear to show the most consistent HPA axis findings. If your long COVID presentation includes post-exertional malaise and unrefreshing sleep in addition to fatigue, the cortisol rhythm disruption findings are most directly relevant to your situation.

Advocate for appropriate testing if symptoms warrant. If you have symptoms that could be consistent with adrenal insufficiency — severe fatigue, dizziness on standing, unexplained weight loss, salt craving, hyperpigmentation — you should ask your doctor about formal adrenal function testing, not because most long COVID patients have this problem, but because it can be missed and it is treatable.

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Frequently Asked Questions

Does long COVID cause low cortisol or high cortisol?

The evidence suggests neither a simple "low" nor "high" cortisol pattern characterizes long COVID overall. The most consistent finding from the highest-quality recent studies is a disrupted circadian rhythm: support healthy cortisol in the morning and higher cortisol in the evening, alongside elevated ACTH signaling. Among patients assessed in a 2025 review, 62.8% had normal cortisol, 36.0% had elevated cortisol, and only 1.2% had low cortisol — suggesting that elevated or normally-ranged cortisol is more common than low cortisol at any given measurement point.

Can cortisol levels diagnose long COVID?

Not reliably, with currently available clinical tests. A standard morning blood cortisol test will appear normal for the vast majority of long COVID patients, because the abnormality in most patients appears to be circadian pattern disruption rather than overall deficiency. Research-grade serial salivary cortisol measurements alongside ACTH show promise for characterizing HPA axis function in long COVID, but these are not yet clinically standardized as diagnostic tools.

Is morning cortisol more informative than random cortisol?

Yes, substantially. Cortisol changes dramatically across the morning. A precisely timed 8–9 AM measurement may detect differences in the cortisol awakening response that are obscured by broader collection windows. The 2024 preprint found no overall difference with broad morning timing but did find lower 8–9 AM cortisol in the ME/CFS-overlap subgroup. Even better than a single morning measurement is a standardized multi-timepoint collection that captures the awakening response curve.

Does long COVID affect the HPA axis or adrenal function?

Current evidence suggests long COVID affects the HPA axis (the brain-adrenal signaling system) rather than the adrenal glands themselves. The 2026 salivary study's finding of elevated ACTH with disrupted cortisol rhythm points to central dysregulation. Multiple studies have reported preserved adrenal function. The adrenal gland appears to still be capable of producing cortisol when stimulated; the problem is in the timing and regulation of that stimulation.

Are salivary cortisol tests better than blood tests for long COVID?

For detecting circadian rhythm disruption, yes. Salivary cortisol measures free biologically active cortisol, can be collected at multiple home time points without the confounders of venipuncture stress, and is not affected by cortisol-binding globulin changes that may accompany inflammation. The highest-quality long COVID cortisol research — including the 2026 circadian study — has used salivary measurements. Standard blood cortisol tests remain appropriate for ruling out frank adrenal insufficiency but are not sensitive to the circadian dysregulation most characteristic of long COVID.

Can cortisol predict fatigue, brain fog, or post-exertional malaise in long COVID?

Research is ongoing, but the biological mechanisms linking circadian cortisol disruption to these symptoms are well-supported theoretically. Blunted morning cortisol impairs energy mobilization, alerting signaling, and circadian synchronization. Elevated evening cortisol disrupts sleep architecture and repair processes. Both patterns are relevant to fatigue and cognitive impairment. Whether individual cortisol measurements predict symptom severity within long COVID samples has not been conclusively established.

Do corticosteroids help long-COVID symptoms if cortisol is abnormal?

For the small minority of patients with confirmed adrenal insufficiency and genuinely low cortisol, cortisol replacement therapy is medically indicated and should be prescribed and monitored by an endocrinologist. For the majority of long COVID patients whose cortisol is in range or elevated, empirical corticosteroid treatment is not supported by current evidence and carries significant risks. The circadian disruption pattern that characterizes most long COVID HPA axis findings is not treated by simply adding more cortisol.

Why do some studies find low cortisol while others find no difference?

The main reasons are: measurement timing (cortisol changes rapidly across the morning and the circadian day); measurement method (salivary vs. blood capture different things); patient subgroup heterogeneity (ME/CFS overlap patients show the most consistent findings); single-point vs. multi-point sampling (circadian disruption is missed by static measurements); and variation in time since infection (HPA axis dynamics may evolve over the course of long COVID). All of these sources of variation can produce apparently contradictory results across studies that are actually measuring different aspects of the same underlying dysregulation.

Summary and Key Takeaways

The field of cortisol and post-COVID research has matured substantially in 2024 through 2026, and the emerging picture is considerably more nuanced than early reports suggested. Here is what the current science most confidently supports:

1. Long COVID is associated with circadian cortisol disruption — not simply low or high cortisol, but a flattened rhythm with reduced morning and elevated evening cortisol, alongside elevated ACTH, as demonstrated by the 2026 salivary circadian study

1. Population-level null results do not rule out subgroup effects — the 2024 preprint's finding of no overall morning cortisol difference coexists with evidence of altered dynamics in the ME/CFS-overlap subgroup

1. The adrenal gland is probably not the primary problem — multiple lines of evidence point toward central HPA axis dysregulation rather than adrenal damage

1. Measurement methodology dramatically affects findings — serial salivary cortisol with ACTH is more sensitive than single-point blood draws for detecting the circadian disruption pattern

1. Cortisol cannot currently diagnose long COVID but may help characterize biological subgroups and rule out adrenal insufficiency

1. Corticosteroid treatment is not supported for most long COVID patients based on current evidence

1. Circadian lifestyle interventions targeting cortisol rhythm normalization have theoretical support and safety advantage

The science is still developing rapidly. The contrast between the 2024 null result and the 2026 circadian finding illustrates how much methodology matters, and how quickly the field can advance when measurement approaches improve. For patients, clinicians, and researchers, the central lesson may be that the HPA COVID story is not about whether cortisol is abnormal, but about when and how it is abnormal — a distinction that standard clinical testing has not yet been designed to capture.

This content is for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider for medical concerns related to long COVID or adrenal function.