What Causes Multiple Sclerosis-Related Fatigue?

Medically Reviewed by Carmelita Swiner, MD on March 02, 2023

Fatigue is the most common symptom of multiple sclerosis (MS). MS fatigue is different from normal tiredness. It saps all your energy and doesn’t go away, even after a good night’s rest. It can make it hard to get through a day of school or work.

Doctors still aren’t sure what causes MS fatigue. It’s probably due to many things, including some tied directly to your MS and others that are results of your MS.

When your fatigue comes directly from your MS, it's called primary fatigue. A couple of things can cause it.

Inflammation. When you have MS, your immune system releases proteins called cytokines that trigger inflammation. That can bring fatigue. It can get worse during relapses, when your body makes more cytokines. If your energy saps quickly, it could be a sign that your MS is about to flare.

Nerve damage. MS damages nerves that send signals to and from your brain. Because of that damage, you may need to use more parts of your brain or think harder than someone who doesn’t have the disease.

When things outside your MS make you feel worn down, it's called secondary fatigue. A lot of things can cause it, including:

Anxiety and depression. When you have MS, changes in your brain can make you feel sad and worried, which can wear you out.  And constant fatigue can make you sad and worried. It’s a vicious cycle that can be hard to break.

Sleep disorders. Lots of people with MS have trouble falling or staying asleep. The disease can damage parts of your brain that control your sleep-wake cycle. Conditions like sleep apnea, restless legs syndrome, and bladder problems can also keep you up at night.   

Other health problems. Many conditions besides MS can cause fatigue. They include:

  • Diabetes
  • Heart disease
  • Anemia
  • A sluggish thyroid gland

Heat. MS affects the part of your brain that controls your body’s temperature. So it’s easy to get overheated. Even a small rise in body temperature can make fatigue and other symptoms worse.

Medication side effects. Many prescription and over-the-counter (OTC) drugs can make you drowsy. This includes some MS meds and OTC sleeping pills. Keep track of all the medicines you take, and tell your doctor about all the side effects that you feel.   

Lack of motivation. It’s hard to work out when you’re worn out. But exercise is one of the most important parts of MS treatment. It improves your fitness and makes your arms and legs stronger. The more strength you have, the less energy it will take you to do routine tasks. Exercise also gives you a boost during the day and helps you sleep better at night. Talk with your doctor about which activities are best for you.

Stress. MS adds an extra layer to everyday pressures. Try to find ways to relax. Yoga, meditation, music, or a walk are good places to start.

Though fatigue is a part of MS, don’t be afraid to mention it to your doctor. There are treatments that can help. You can also do a lot to feel more energetic by making healthy lifestyle choices:

  • If you smoke, stop.
  • Get plenty of exercise.
  • Eat a low-fat, mainly plant-based diet.
  • Find healthy ways to ease stress.
  • Keep cool, with things like air conditioning, cool showers, and cooling vests.

Show Sources


Brain Sciences: “Fatigue and Affective Manifestations in Multiple Sclerosis—A Cluster Approach.”

Disease Markers: “Fatigue in Patients with Multiple Sclerosis: Is It Related to Pro- and Anti-Inflammatory Cytokines?”

Cleveland Clinic: “Multiple Sclerosis: Fatigue.”

National Multiple Sclerosis Society: “Fatigue,” “But You Look So Good,” “Fatigue: What You Should Know: A Guide for People with MS,” “Sleep Disturbance and Multiple Sclerosis.”

Frontiers in Neurology: “The Representation of Inflammatory Signals in the Brain – A Model for Subjective Fatigue in Multiple Sclerosis.”

Nervenartz: “Therapy of Fatigue in Multiple Sclerosis: A Treatment Algorithm.”

Sleep Medicine: “Hypnotic use and fatigue in multiple sclerosis.”

Penn Medicine: “Multiple Sclerosis and Exercise: Why MS Patients Should Stay Active.”

EPMA Journal: “The Berlin Treatment Algorithm: Recommendations for tailored innovative therapeutic strategies for multiple sclerosis-related fatigue.”

Multiple Sclerosis and Related Disorders: “Low-fat, plant-based diet in multiple sclerosis: A randomized, controlled trial.”

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