Abundant evidence suggests that sleep might be altered during infectious disease, although the relationship between sleep and infectious disease has never been examined systematically. To address this issue, we determined the effects of Staphylococcus aureus infection on rabbit sleep. Rabbits inoculated intravenously with S. aureus demonstrated the expected physiological changes consistent with a state of infectious disease (e.g., lymphopenia, neutrophilia, and fever), as well as time-dependent changes in sleep patterns. The sleep changes were characterized initially by increases in (i) the time spent in slow-wave sleep, (ii) the electroencephalographic slow-wave amplitudes during slow-wave sleep, and (iii) the duration of individual bouts of slow-wave sleep. At 20 to 36 h after inoculation, sleep responses fell to levels below corresponding control values for 6 to 12 h. At 6 to 10 h after inoculation, rapid-eye-movement sleep was suppressed and remained at low levels throughout the remainder of the 48-h recording period. These effects of bacterial infection on sleep were attenuated by antibiotic (cephalothin) therapy. Inoculation with killed bacteria produced similar changes in sleep and other physiological parameters, although significantly higher numbers of organisms were required to produce equivalent responses. We postulate that changes in sleep may represent an adaptive response of the host to infectious disease.