The study evaluated the effects of different anesthetics on the hepatic oxygen supply-demand relationship and hepatic lactate uptake (HLu). Miniature pigs (n = 33), weighing 20–31 kg, were divided into five groups and accordingly anesthetized with halothane, isoflurane, enflurane (0.9%, 1.5%, and 2.2% end-expired concentrations, respectively), fentanyl (100 μg/kg iv bolus followed by a continuous infusion of 50 μg · kg−1· h−1), or sodium pentobarbital (30 mg/kg iv bolus followed by a continuous infusion at a rate of 1–2 mg · kg−1· h−1). The surgical preparation allowed the authors to induce a stepwise decrease in hepatic blood supply without congestion in the preportal tissues. Prior to induced hepatic hypoperfusion, the values of hepatic oxygen delivery (HDO2) were the greatest in the isoflurane and fentanyl groups and the smallest in the halothane group, while the values of hepatic oxygen uptake (HVO2) were the smallest in the halothane group without differences among the other four groups. During stepwise decrease in hepatic blood and oxygen supply, HLu started to decrease at higher values of hepatic oxygen delivery in the fentanyl group (HDO2= 10 mlO2· min−1·100 g−1) than in all others (HDO2=6–7 mlO2· min−1·100 g−1). At values of HDO2equal to 2–3 mlO2· min-1· 100 g−1, the values of HLu became negative, signifying that the liver began to release rather than to metabolize lactate. There was a linear relationship between the values of HDO2and hepatic venous oxygen tension or saturation (r = 0.96;P< 0.001). Among the five anesthetics studied, isoflurane and fentanyl provided the greatest values of HDO2and hepatic venous oxygen supply-demand ratios. Halothane decreased hepatic oxygen demand and could have provided some protection from hepatic oxygen deprivation. However, the decrease in hepatic oxygen delivery produced by halothane was greater than the decrease in hepatic oxygen demand; therefore, halothane might not be the anesthetic of choice for surgical procedures where hepatic hypoxia is anticipated. Oxygen saturation in hepatic venous blood is an indicator of adequacy of hepatic oxygen supply.