Inoculation of rats with microorganisms or microbial constituents that activate host defense promotes non-rapid eye movement sleep (non-REMS) and suppresses REMS. In this study, we evaluated circadian influences on the effects of lipopolysaccharide (LPS) on sleep, sickness behavior and plasma corticosterone levels in the rat. Three sets of experiments were performed. In each, the animals were intraperitoneally injected with vehicle for LPS (30 µg/kg) during 2 consecutive days, at the beginning of either the circadian rest or the activity phase. In experiment 1, sleep-wake behavior and brain temperature were recorded, and in experiment 2, core body temperature, locomotor activity as well as food and water intake. In experiment 3, corticosterone blood levels were measured. The results show that LPS-evoked changes in temperature, sleep and other behavioral parameters depend markedly on the time of day LPS is administered. However, a direct comparison of the LPS data demonstrates that, except for sleep parameters, the absolute time course of the assessed parameters was rather similar between the rest and activity phases. These findings suggest that LPS evokes a state characterized by high temperature and low vigilance, which is reached independently of the circadian phase.