When Rest Isn’t Enough: How to Break the Vicious Cycle of Fatigue.
Have you ever felt jet-lagged without flying? For people with Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME), that feeling can be a daily reality.
Imagine waking up exhausted, slogging through the day as if your internal battery never charges, and crashing even harder after simple tasks. CFS is more than just “being tired”: it’s a complex condition defined by persistent, disabling fatigue that doesn’t improve with rest, along with “post-exertional malaise” (PEM) – a severe crash in energy after physical or mental exertion. Sufferers often grapple with unrefreshing sleep, brain fog, and a host of other symptoms. While the exact cause remains a mystery, a growing body of research is exploring one intriguing piece of the puzzle: circadian rhythm disruption. In plain terms, problems with the body’s internal clock- and how it might be fuelling the fatigue.
Every cell in your body has a schedule. In a healthy rhythm, days are for alertness, activity, and energy; nights are for rest, repair, and recovery. Key hormones rise and fall on this schedule: for example, cortisol (a hormone that boosts energy and alertness) surges in the early morning, helping us wake up, while melatonin is released after dark. These hormonal cycles keep our sleep-wake pattern running smoothly and influence everything from body temperature to immune function.
Now, imagine what happens if this careful timing falls out of sync. If your body’s clock thinks day is night and night is day, you get internal chaos. In the context of CFS, researchers are asking: Could a perpetual clock error be one reason patients can’t recharge, no matter how much they rest?
It turns out that many hallmarks of CFS, poor sleep, extreme fatigue, brain fog, and PEM, overlap with symptoms you might experience if your circadian rhythm is broken. This has led scientists to investigate CFS through the lens of circadian biology. Although it’s an evolving field¹, several recent studies have uncovered intriguing connections between circadian disruptions and CFS:
Light Exposure: The Body’s Time Cue
Light is the principal time-setter for our circadian clock. Interestingly, a 2018 study tracking CFS patients found they were getting less daily light exposure than healthy people². These patients lacked the typical midday rise and nighttime drop in body temperature seen in others – a sign that their internal rhythms were out of sync. The researchers suggest that being indoors and inactive (as many with CFS often are) could blunt the light signals that normally anchor the internal clock². In other words, insufficient daylight might be exacerbating the body’s timing problems. It’s no surprise, then, that when CFS patients were given light therapy, their sleep improved².
Hormonal Rhythms: Cortisol and Melatonin
In healthy individuals, cortisol spikes at sunrise – think of it as nature’s caffeine – and melatonin peaks at night. In CFS, these rhythms can go awry. Some studies have found that CFS patients show an oddly flattened cortisol cycle, lower variability between morning and evening levels³. This blunting of the cortisol rhythm could contribute to that all-day drained feeling. There’s also evidence of abnormal timing in the production of melatonin. One small trial discovered that a subgroup of CFS patients who had delayed melatonin release in the evenings, essentially, their brains got the “it’s night, time to sleep” signal later than normal, benefited from nightly melatonin supplements, experiencing reduced fatigue⁴. The finding suggests that for some, CFS might involve a circadian phase delay (a body clock running slow or late), and correcting that timing could help. On the flip side, other studies on melatonin levels in CFS have been mixed: some patients show normal melatonin, and others have elevated nighttime levels⁴, so research is ongoing. But clearly, how and when these hormones cycle in CFS is a crucial piece of the puzzle.
Sleep Timing and “Wired-and-Tired” Cycles
Sleep problems are almost universal among people with CFS. Many experience insomnia (despite bone-deep fatigue) and may end up oversleeping or napping at odd times to catch up. This irregular sleep-wake pattern can further confuse the internal clock. Some experts hypothesize a vicious cycle: insomnia leads to late wakeups or excessive napping, which in turn shifts the circadian rhythm out of phase, so your cortisol peak might occur later than it should, leaving you groggy in the morning⁵. One study observed CFS patients across daily life and noted greater variability in their activity and body temperature rhythms, suggesting a loss of synchronized timing between the brain’s clock and the rest of the body². This kind of circadian disarray could mean that sleep isn’t happening at the biologically optimal time, resulting in sleep that isn’t restorative. It may also mean that when a person with CFS exerts themselves, it could be at a time of day when their body is least prepared to handle it, possibly worsening that dreaded post-exertional malaise.
The picture emerging from these findings is that circadian rhythm disruption is both a cause and effect of CFS. Fatigue leads to irregular habits (avoiding light, inconsistent sleep) that disrupt the clock, and a disrupted clock in turn, produces more fatigue⁶. It’s a destabilizing feedback loop. One researcher described it as “having a broken clock that can’t tell time, and every system in your body shows up to work at the wrong time.” Over weeks, months, and years, this can accumulate to profound exhaustion. Unsurprisingly, scientists are now also looking at long COVID, a condition with symptoms very similar to CFS, and finding that the SARS-CoV-2 virus may throw off our cellular clock genes and hormones, contributing to long-lasting fatigue⁷. In fact, a 2025 Lancet review highlighted circadian disturbances as a key factor in long COVID’s fatigue and sleep issues, reinforcing the idea that when our biology does its work is crucial for recovery⁷.
What This Means for You
For one, it validates what patients have long felt: there is a biological timing component to their illness. CFS isn’t “in your head”; it’s in your cells and hormones, possibly misfiring at the wrong hours. This understanding also opens the door to new strategies. Doctors and scientists are now exploring “chronotherapy,” which is treatment aimed at restoring proper timing to the body’s systems.
There is a hopeful message here: at least some aspects of this illness might be manageable. Lifestyle tweaks like getting morning sunlight and keeping a consistent sleep routine could make a tangible difference in day-to-day energy.
These changes may not solve everything overnight. But by tuning into your internal clock, you could start seeing improvements in sleep quality, energy, mood, and overall well-being. The science is still evolving, but one thing is clear: When you live in sync with your body’s natural rhythm, you’re giving yourself a better shot at feeling like yourself again.
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Dr. Jonathan Moustakis
Co-founder and CTO of Lume Health
Herane-Vives, A., et al. (2020). Cortisol in hair and saliva in patients with chronic fatigue syndrome. Journal of Affective Disorders, 260, 228–232.
Cambras, T., et al. (2018). Circadian rhythm abnormalities and autonomic dysfunction in patients with CFS/ME. PLOS ONE, 13(6): e0198106.
Nater, U.M., et al. (2008). Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. Journal of Clinical Endocrinology & Metabolism, 93(3), 703–709.
van Heukelom, R.O., et al. (2006). Influence of melatonin on fatigue severity in patients with chronic fatigue syndrome with late melatonin secretion. European Journal of Neurology, 13(1): 55–60.
Russell, C., et al. (2016). Subjective but not actigraphy-defined sleep predicts next-day fatigue in chronic fatigue syndrome: A prospective daily diary study. Sleep, 39(4), 937–944.
Butler, M., et al. (2023). A series of personalized virtual light therapy interventions for fatigue: Feasibility randomized crossover trial for N-of-1 treatment. JMIR Formative Research, 7, e45510.
Lockley, S.W., et al. (2025). Post-infectious fatigue and circadian rhythm disruption in long COVID and other infections: A need for further research. EClinicalMedicine, 80, 103073.
