The liver oxygen delivery (DO2) and consumption (VO2) were measured in a porcine model of septic shock induced by fecal peritonitis. Lactate and hypoxanthine were simultaneously monitored in hepatic extracellular fluid and in central venous blood using a microdialysis technique. Animals were divided into a control group (n = 6) and a peritonitis group (n = 6). Peritonitis was induced by installation of a standardized amount of autologous feces into the abdominal cavity. The animals were followed for 5 h. The changes in the liver during peritonitis were, a decreased DO2, a increased, maintained, or decreased VO2, an increased oxygen extraction, and a loss of net hepatic lactate uptake. Parallel to these changes, systemic lactic acidosis developed. Intrahepatic lactate and hypoxanthine increased during peritonitis reflecting liver ischemia. The increase of these metabolites was seen concomitantly in the liver and in central venous blood. There was a wide variability of the individual response to the septic challenge among the animals. The limited hepatic oxygen delivery, and the increased needs for oxygen led to flow-dependent oxygen consumption, and signs of liver ischemia in severe sepsis. Intrahepatic and intravenous microdialysis may be useful for monitoring of the individual time course of hepatic and systemic ischemia in sepsis.