Why the myocardial oxygen extraction ratio (ERm) is decreased during septic shock in humans is unknown. Therefore, we calculated ERm in 15 anesthetized pigs by measuring arterial and coronary venous oxygen content. We measured myocardial lactate flux, myocardial contractility, and global myocardial blood flow and its distribution. After baseline measurements, animals received either saline (n = 6) or 50 micrograms/kg of endotoxin (n = 9). Measurements were repeated for 4 h. After endotoxin, ERm decreased from 67 +/- 12% at baseline to 36 +/- 10% (P < 0.01) at 1 h and 54 +/- 10% (P < 0.05) at 4 h, associated with an increased myocardial blood flow that was heterogeneous. Neither myocardial oxygen nor lactate consumption decreased in the endotoxin group, and changes in left ventricular contractility were not correlated with changes in ERm. We conclude that the decrease in ERm after endotoxin infusion is due to both increased blood flow and mismatching between myocardial oxygen delivery and demand. Impaired myocardial oxygen extraction capacity during sepsis did not cause global myocardial tissue hypoxia.