Purpose: The cardiovascular effects of volatile anesthetics during sepsis sets patients at high risk for hemodynamic deterioration. We compared the microcirculatory alterations in skeletal muscle under anesthesia with isoflurane, enflurane, and halothane in an endotoxemic rat preparation. Materials and Methods: Twenty-one Sprague-Dawley rats under continuous hemodynamic monitoring and intravital microscopy of the spinotrapezius muscle were studied during two level lipopolysaccharide (0.2 mg/kg and 2 mg/kg) induced sepsis. The effects of equianesthetic concentrations (1.5 minimum alveolar concentration [MAC]) of either isoflurane [n:7], enflurane [n:7], or halothane [n:7] on microcirculatory vasoregulation were measured and histopathologic changes were evaluated. Results: During low-dose endotoxemia, arteriolar vasodilation under isoflurane was nearly abolished (P < .05). At high-dose endotoxemia, this lack of vasodilatory effect was similar (P < .05). Animals receiving 1.5 MAC of enflurane during lowdose endotoxin presented a significant decrease in arteriolar diameter by -11.3 (±2.9%), this response was less during high-dose endotoxemia (-7.0, ±2.9%). Halothane caused pronounced vasoconstriction by -20 (±3.7%) during low-dose endotoxemia and moderate but significant constriction during high-dose endotoxemia (-7.9, ±2.6%). Conclusions: Isoflurane, enflurane, and halothane exert significantly different effects on vasoregulation of skeletal muscle arterioles in the endotoxemic rat.