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Does inflammation cause fatigue?

Written on March 29, 2023 by Gillian (Gigi) Singer, MPH. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

Table of contents

About inflammation

Inflammation is the body’s natural response to harmful stimuli, such as infections or injuries. While acute inflammation is beneficial in fighting off infections and repairing tissue damage, chronic inflammation has been linked to a variety of health problems, including fatigue.

Inflammation is a complex process that involves the release of various chemical messengers, such as cytokines, which trigger an inflammatory response. While inflammation is a necessary mechanism for healing and fighting off infections, chronic inflammation can have detrimental effects on the body, including fatigue.

Defining fatigue

When you’re sick, you often feel tired and/or sleepy — this is an example of fatigue. Your body is working hard to heal itself, so it makes sense if you need more sleep than you normally do. Nearly everyone experiences fatigue “during short-term illness,” and fortunately, “fatigue usually goes away when the illness is over” [1].

However, sometimes, fatigue lingers and doesn’t go away, no matter how much rest you get, and the cause may be unclear. The Mayo Clinic asserts, “fatigue reduces energy, the ability to do things, and the ability to focus. Ongoing fatigue affects quality of life and state of mind” [1].

Chronic fatigue syndrome

While short-term fatigue is common and a normal bodily response, chronic fatigue syndrome (CFS) is altogether different. Also called myalgic encephalomyelitis (ME/CFS), CFS “causes extreme fatigue that lasts for at least six months” and “symptoms worsen with physical or mental activity but don’t fully improve with rest” [2]. Its cause is unknown, and the following symptoms may accompany it:

  • Extreme exhaustion after physical or mental exertion
  • Memory or cognitive problems
  • Dizziness that is worse when going from moving to lying down or from sitting to standing
  • Muscle and/or joint pain
  • Feeling unrefreshed after sleeping
  • Headache
  • Sore throat
  • tender lymph nodes in the neck or armpits
  • Sensitivity to light, sound, smells, food, and/or medicines

Causes of fatigue

There are numerous potential causes of fatigue, which you can also read about in our other article, “Possible causes of inflammation — and related health conditions.”

How inflammation contributes to fatigue

According to a 2018 study, “It is well known from experimental studies that acute severe inflammation… causes acute sickness behavior, including fatigue” [3].

They continue to explain that inflammation as a response to sickness or infection is an adaptive process (a physiological response that has developed as a result of something) that aids in “the conservation of energy and reduction of the risk of further dissemination of pathogens (eg, by withdrawing from social interactions)” [3].

Below are some specific ways in which inflammation contributes to fatigue:

  1. Increased energy demands: Inflammation triggers the release of cytokines, which stimulate the production of energy in cells [4]. This process requires energy from the body, which leads to fatigue.
  2. Disrupted sleep: Chronic inflammation can disrupt the normal sleep-wake cycle, leading to poor quality sleep and increased fatigue [5]. This disruption is caused by the release of cytokines that activate the central nervous system, making it difficult to fall asleep and remain asleep.
  3. Muscle fatigue: Inflammation can also cause muscle fatigue, which is characterized by a feeling of weakness and tiredness [6]. This occurs when the inflammatory response triggers the production of chemicals that cause muscle cells to become less efficient at producing energy.
  4. Cognitive fatigue: Inflammation may affect brain function, leading to cognitive fatigue [7]. This type of fatigue is characterized by difficulty concentrating, problems with memory, and feeling mentally exhausted. This occurs when cytokines cross the blood-brain barrier and interfere with the normal functioning of brain cells.
  5. Hormonal imbalances: Chronic inflammation can also disrupt the balance of hormones in the body, leading to fatigue [8]. For example, inflammation can increase the levels of the stress hormone cortisol, which can cause fatigue and a feeling of being "burned out.”
  6. Autoimmune disorders: Autoimmune diseases occur when “the immune system malfunctions” and “it mistakenly attacks healthy cells, tissues, and organs… these attacks can affect any part of the body, weakening bodily function and even turning life-threatening” [9]. Autoimmune diseases, such as multiple sclerosis, diabetes, and rheumatoid arthritis, are associated with increased levels of fatigue due to “an increase in plasma cytokines, especially during symptom relapse” [3].

Testing for inflammation

Everlywell’s Inflammation Test uses high-sensitivity CRP (hs-CRP) testing to test you for inflammation which can give you great insight into your health. Check out our quick guide, “How to test for inflammation,” for more information.

Acute vs. chronic inflammation: understanding the difference

6 possible signs of inflammation in the body

Foods and inflammation: how do foods cause inflammation?


  1. Mayo Clinic. Fatigue. URL. Published February 11, 2023. Accessed March 22, 2023.
  2. Mayo Clinic. Chronic fatigue syndrome. URL. Published January 21, 2023. Accessed March 22, 2023.
  3. Lacourt TE, Vichaya EG, Chiu GS, Dantzer R, Heijnen CJ. The high costs of low-grade inflammation: persistent fatigue as a consequence of reduced cellular-energy availability and non-adaptive energy expenditure. Front Behav Neurosci. 2018;12:78. doi:10.3389/fnbeh.2018.00078. URL.
  4. Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008. doi:10.3390/ijms20236008. URL.
  5. Milrad SF, Hall DL, Jutagir DR, et al. Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women. J Neuroimmunol. 2017;303:43-50. doi:10.1016/j.jneuroim.2016.12.008. URL.
  6. National Institute of Neurological Disorders and Stroke. Inflammatory myopathies. URL. Accessed March 22, 2023.
  7. National Gaucher Foundation. How systemic inflammation affects your brain & central nervous system. URL. Published March 24, 2022. Accessed March 22, 2023.
  8. Straub RH. Interaction of the endocrine system with inflammation: a function of energy and volume regulation. Arthritis Res Ther. 2014;16(1):203. doi:10.1186/ar4484. URL.
  9. National Institute of Environmental Health Sciences. Autoimmune diseases. URL. Accessed March 22, 2023.
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