We examined the effects of sevoflurane pretreatment on mortality and inflammatory responses during endotoxin-induced shock. Rats were allocated randomly to 1 of 4 groups (n = 12 per group): an endotoxemia group, receiving IV Escherichia coli endotoxin (15 mg/kg over 2 min); a saline control group, receiving 0.9% saline (1.0 mL/kg); a sevoflurane-only group, receiving 2.4% sevoflurane for 30 min immediately before injection of 0.9% saline; and a sevoflurane pretreatment group, receiving 2.4% sevoflurane for 30 min immediately before injection of endotoxin. Hemodynamic variables, arterial blood gases, and plasma concentrations of tumor necrosis factor-alpha and interleukin-6 were measured. The 8-h mortality rate was determined. Systolic arterial blood pressure and acid-base balance improved with sevoflurane pretreatment before induction of endotoxemia. Mortality rates 8 h after endotoxin injection were 83%, 8%, 0%, and 25% for the endotoxemia, saline control, sevoflurane-only, and sevoflurane pretreatment groups, respectively. Plasma cytokine concentrations were significantly larger in the endotoxemia group than in the other groups. Sevoflurane pretreatment inhibited inflammatory responses and decreased mortality in rats exposed to endotoxin. CONCLUSIONS Sevoflurane pretreatment decreased mortality rate, severity of hypotension, and acidosis, and inhibited cytokine responses in rats injected with endotoxin, suggesting that sevoflurane may be an anesthetic of choice in endotoxemic states.