Neurological abnormalities including agitation, confusion, disorientation, lethargy, and obtundation are early characteristic findings in patients with sepsis. The etiology of the changes in mental status that occur during severe infection is unknown. We investigated the effects of sepsis on intermediary metabolism and bioenergetics in the brain during normoxia and moderate hypoxia (8% inspired O2 concentration) in rats 36-42 hr following cecal ligation and perforation. The rats were anesthetized with halothane, and brains frozen using the funnel-freezing technique. Perchloric acid extracts of brains were analyzed with fluorometric enzymatic methods and 31P nuclear magnetic resonance spectroscopy. There was no impairment in bioenergetics or intermediary metabolism in septic brain, and sepsis did not compromise the ability of the brain to maintain high-energy phosphates during hypoxia. Hypoxia did cause the brain lactate-to-pyruvate ratio to increase equivalently in both septic and control rats from approximately 9:1 to 20:1 (P < 0.001). We conclude that the neurologic changes which are characteristic of sepsis are unlikely to be due to alterations in cellular energy stores or intermediately metabolism. In addition, there is no evidence that sepsis results in brain cellular hypoxia.