It’s normal to feel wiped out after a hectic week, a poor night’s sleep or a lingering cold. But for some people, exhaustion isn’t something that goes away after rest. It becomes a constant companion that can reshape everyday life.

These individuals may struggle to concentrate at work, keep up with social commitments or even find it difficult to perform basic tasks without feeling depleted. For them, fatigue isn’t simply tiredness; it’s a profound, body-wide shutdown that doesn’t respond to coffee, naps or willpower.

This often-misunderstood condition is known as chronic fatigue syndrome, a complex illness that researchers are only beginning to fully untangle.

Here’s what it is, why it happens and how people diagnosed with it can find relief.

What is chronic fatigue syndrome?

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a long-term, multisystem illness characterized by deep, persistent fatigue that is not improved by rest and is severe enough to interfere with daily activities. "The core of this illness manifests as a severe and incapacitating fatigue that lasts for over six months," says Dr. Hector Bonilla, a clinical professor of medicine and an infectious disease specialist at Stanford Health Care.

As many as 3.3 million people living in the United States struggle with the condition, according to the U.S. Centers for Disease Control and Prevention, though many people aren't diagnosed with it because CFS is often misunderstood or confused with other health issues.

Another difficulty in diagnosing is due to CFS symptoms overlapping with conditions such as depression, hypothyroidism, fibromyalgia, anemia, autoimmune disorders and sleep apnea. These other causes often also need to be ruled out. What's more, there is no blood or biomarkers test for CFS, says Bonilla, so clinicians have to rely on a detailed medical history for the patient, symptom pattern and pre-established clinical criteria.

The hallmark symptom of CFS, notes Bonilla, is “post-exertional malaise,” a delayed crash in energy and function that occurs after even minimal physical or mental activity. People describe this crash as feeling flu-like, heavy, cognitively foggy or completely depleted, often taking days or longer to recover. Other common symptoms of CFS include "dizziness, muscle and joint pain, poor sleep and memory problems," explains Dr. Neha Vyas, a family medicine physician at Cleveland Clinic. "Sometimes we also see exercise intolerance and reduced peak oxygen consumption."

Many patients also experience autonomic nervous system issues, such as rapid heartbeat when standing.

What causes chronic fatigue syndrome?

The exact cause of CFS remains unknown, but research increasingly points toward a combination of biological triggers and chronic dysregulation in multiple body systems. "Over 60% of patients refer to a past infectious process that triggered the illness," says Bonilla. Such infections commonly include Epstein-Barr virus, influenza or, more recently, COVID-19. "The herpes virus, enterovirus and retrovirus are other viruses that have been implicated in this condition," adds Vyas.

Such viruses and infections may contribute to CFS, Bonilla explains, by disrupting immune signaling, energy metabolism and autonomic nervous system function in ways that persist long after the initial illness resolves.

Genetic predisposition may also play a role, says Vyas, as research indicates that people with a family history of autoimmune or immune-related disorders may be at higher risk of developing CFS. Hormonal imbalances, particularly involving cortisol regulation, have been observed as well, though researchers are still determining whether these are causes or consequences of the condition.

Some people also develop CFS after physical trauma, significant stress or environmental exposures, suggesting other possible pathways for the condition's development.

How is CFS treated?

There is currently no cure for CFS, but effective management can significantly improve quality of life. Because the condition varies widely, "treatment focuses on symptom management, improving sleep quality, coping with pain and cognitive symptoms and finding ways to boost daily functioning," says Vyas.

Medical treatments may include medications to manage pain, sleep disturbances, dizziness or depression, as well as therapies for related conditions like POTS or allergies. Specifically, some patients benefit from low-dose naltrexone, antihistamines or targeted antiviral or immune-modulating treatments, though evidence varies and should be supervised by a specialist.

Cognitive support strategies such as memory aids or occupational therapy can also help with daily functioning. Nutrition guidance is common as well, notes Bonilla, including eating more whole foods, lean proteins and anti-inflammatory fruits and vegetables, while reducing processed foods and added sugars that may worsen inflammation or cause energy crashes.

At home, one of the most important interventions is pacing, Bonilla explains. This approach involves carefully tracking energy levels, recognizing early signs of overexertion and balancing rest with activity to avoid triggering crashes. Gentle stretching, hydration and sleep-stabilizing routines may also ease symptoms, though intense exercise is typically discouraged because it can worsen post-exertional malaise.

Many patients also find relief through mindfulness practices, breathing exercises, relaxation techniques or support groups that provide emotional and practical guidance.

Bonilla says a doctor can help tailor specific patient recommendations and rule out other illnesses, and coordinate testing and treatment needs.

While Vyas says that CFS "is a complex and challenging illness we're still learning more about," many people diagnosed with it learn to manage symptoms more effectively over time. And with emerging research and growing awareness, there is real hope that better treatments – and clearer answers – are on the horizon.

This article originally appeared on USA TODAY: Chronic fatigue syndrome drains millions of people, and still defies easy answers

Reporting by Daryl Austin, USA TODAY / USA TODAY

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