The objective of this study was to evaluate the effects of nocturnal sleep, partial night sleep deprivation, and sleep stages on circulating concentrations of interleukin-6 (IL-6) in relation to the secretory profiles of GH, cortisol, and melatonin. In 31 healthy male volunteers, blood samples were obtained every 30 min during 2 nights: uninterrupted, baseline sleep and partial sleep deprivation-early night (awake until 0300 h). Sleep was measured by electroencephalogram polysomnography. Sleep onset was associated with an increase in serum levels of IL-6 (P < 0.05) during baseline sleep. During PSD-E, the nocturnal increase in IL-6 was delayed until sleep at 0300 h. Sleep stage analyses indicated that the nocturnal increase in IL-6 occurred in association with stage 1-2 sleep and rapid eye movement sleep, but levels during slow wave sleep were not different from those while awake. The profile of GH across the 2 nights was similar to that of IL-6, whereas the circadian-driven hormones cortisol and melatonin showed no concordance with sleep. Loss of sleep may serve to decrease nocturnal IL-6 levels, with effects on the integrity of immune system functioning. Alternatively, given the association between sleep stages and IL-6 levels, depressed or aged populations who show increased amounts of REM sleep and a relative loss of slow wave sleep may have elevated nocturnal concentrations of IL-6 with implications for inflammatory disease risk.