Sickness often brings on fatigue. But why do we feel so tired when we are sick? “There’s not a simple answer,” said James Krueger, a neuroscientist at Washington State University who studies how sleep relates to infectious disease. 

To better understand this sickness-related fatigue, scientists like Krueger study the molecules from pathogens and the immune system that cause sleep during an illness. In the early 1980s, Krueger isolated muramyl peptide, a component of bacterial cell walls, from human urine samples and showed that it induced sleep in rabbits.1 

Muramyl peptide induces interleukin-1β (IL-1β), a cytokine that is part of an inflammatory response. With collaborators who were studying IL-1β, Krueger found that this cytokine also caused rabbits to sleep.Additional studies from other teams showed that IL-1β also correlates with sleeping behavior in humans.3-5 Researchers also identified other inflammatory cytokines triggered during infection that induce sleep in animals and humans.6-8 These may work in conjunction with neurotransmitters, genes, and the circadian rhythm, which regulate normal sleep.

One hypothesis for why immune proteins induce sleep alongside their inflammatory roles suggests that sleeping during illness is the body’s way of conserving energy.10 Fevers induced during infection are metabolically demanding.11,12 Additionally, sleep is important for responding to cellular stress, repairing damaged tissues, and even regulating immune cell proliferation and trafficking.13-15

While the exact reasons behind why we tend to sleep more when we’re sick aren’t fully pinned down, the research suggests that it is evolutionarily conserved across species to rest when the body is stressed. 

“Most people’s grandmothers or mothers have told them to get sleep to recuperate from a disease,” Krueger said. “That’s probably good advice.” 


  1. Krueger JM, et al. J. Biol. Chem. 1982;257(4):1664-9
  2. Krueger JM, et al. Am. J. Physio. 1984;246(6)R-994-R999
  3. Hohagen F, et al. Neuropsychobiology 2008;28(1-2):9-16
  4. Vollmer-Conna U, et al. Psychol Med 2004;34(7):1289-1297
  5. Covelli, V et al. Int J Neuro 1992;63(3-4):299-305
  6. Shoham S, et al. Am. J. Physio. 1987;253(1):R142-R149
  7. Hogan D, et al. J. Neuro. 2003;137(1-2):59-66
  8. Späth-Schwalbe E, et al. J. Clin. Endocr. 1998;83(5):1573-1579
  9. Garbarino S, et al. Commun Biol. 2021;4:1304
  10. Imeri L, Opp MR. Nat. Rev. Neurosci. 2009;10(3):199-210
  11. Baracos VE, et al. Can J Physiol Pharmacol. 1987;65(6)1248-1254
  12. Berger RJ, Phillips NH. Behav Brain Res. 1995;69(1-2)65-73
  13. Davis KC, Razien DM. Phsyiol. J. 2016;595(16): 5415-5424
  14. Elkhenany H, et al. Life Sci. 2018;214(1):51-61
  15. Besedovsky L, et al. Eur J Appl Physiol. 2012;463:121-137

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