Sleep regulates inflammatory responses, and the innate immune system affects sleep. Interleukin-1 beta, tumor necrosis factor alpha, growth hormone-releasing hormone, prolactin, and nitric oxide are somnogenic substances. Sleep deprivation, such as chronic insomnia or obstructive sleep apnea, affects cytokine production, glial function, natural killer cell activity, and inflammasome function. This review will discuss the relationship between sleep and innate immunity.