Lighting and other environmental cues in the intensive care unit rarely adhere to a consistent daily pattern. To determine the influence of the daily light/dark (LD) cycle on recovery from sepsis, male Sprague Dawley rats were acclimated to lights-on condition at 6 AM and lights-off condition at 6 PM for 6 to 14 days. Catheter placement and cecal ligation and puncture (CLP) were performed under ketamine and xylazine. Rats were returned to the established LD cycle, to constant light (LL), or to constant dark (DD) at 6 PM. One-week survival was 83.33% during LD (n = 24), 62.5% during LL (n = 16), and 31.25% during DD (n = 16; P < 0.01 for difference from the LD group). Both plasma adrenocorticotropin (ACTH) and corticosterone levels in the morning of the first day after CLP were greater during DD than during LD (P < 0.05 in each case). The early elevation in ACTH was independent of survival. However, the greater frequency of nonsurviving DD rats accounted for the elevation of corticosterone in the DD group. Overall, most nonsurvivors had a unique response pattern composed of an early elevation of corticosterone in relation to plasma ACTH that then declined to a value above the normal circadian peak despite a late increase in endogenous ACTH when death was imminent. We conclude that the circadian cues provided by the LD cycle improve survival after CLP. Removal of these cues by DD increases the early appearance and incidence of a hormonal response pattern that is associated with a lethal outcome.