Animal studies reveal that cytokines play a key role in the regulation of sleep. Alcoholic patients show profound alterations of sleep and a defect in the homeostatic recovery of sleep following sleep loss. In this study, we investigated whether nocturnal plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF) were associated with disordered sleep in alcohol dependence by testing the temporal relationships between these inflammatory cytokines and sleep, before and after sleep deprivation. All-night polysomnography and serial blood sampling at 23:00, 03:00, and 06:30 h were conducted across baseline, partial sleep deprivation, and recovery nights in abstinent African American alcoholics (n=16) and matched controls (n=15). Coupled with prolonged sleep latency and increased rapid eye movement sleep, alcoholics showed nocturnal elevations of IL-6 and TNF as compared to controls after adjustment for alcohol consumption and body mass index. Following sleep deprivation, alcoholics showed greater nocturnal levels of IL-6 and greater nocturnal increases of TNF as compared to controls. Pre-sleep IL-6 levels at 23:00 h correlated with prolonged sleep latency after adjustment for potential confounders whereas IL-6 levels at 03:00 h correlated with rapid eye movement sleep in the second half of the night. Taken together, these findings indicate that circulating levels of proinflammatory cytokines may have a negative influence on sleep initiation. These findings have implications for determining why sleep is disordered in alcoholics and may aid in the development of novel treatments to optimize sleep in this population.