OBJECTIVES: The potential advantages of lowering core temperature during sepsis are to lower energy requirement and to activate various cell-protecting pathways. We experimentally investigated whether postconditioning temperature modifications influence survival duration during experimental sepsis. DESIGN: A prospective, randomized, experimental animal study. SETTING: University laboratory. SUBJECTS: Eighteen male Sprague-Dawley rats (median 326 g, range 310-347 g). INTERVENTIONS: After anesthesia, experimental sepsis was induced by cecal ligation and perforation. The animals were subsequently assigned a core temperature range: normothermia (37 degrees C), hyperthermia (42 degrees C), and mild hypothermia (32 degrees C). Anesthesia and analgesia were continuously maintained until death. MEASUREMENTS AND MAIN RESULTS: Plasma lactate and pyruvate concentrations were measured at sepsis induction (H0), 4 hrs later (H4), and/or at the time of death. A significant increase in lactate concentration was observed at the time of death in the 42 degrees C group (p = .04). Lactate-to-pyruvate ratio increased in the 32 degrees C (at H4) and 42 degrees C (at the time of death) groups (p = .04). A linear correlation between a longer survival duration and a lower assigned core temperature was observed (from 61 +/- 10 mins at 42 degrees C to 289 +/- 17 mins at 37 degrees C and to 533 +/- 69 mins at 32 degrees C; R = .959, p < .0001). CONCLUSIONS: The current results demonstrate that postconditioning hypothermia was associated with increased survival duration during experimental sepsis. Whether the observed benefits on survival duration are due to potential impacts on energy metabolism or to an anti-inflammatory effect of hypothermia requires further investigation.