We studied the effects of diaspirin cross-linked hemoglobin (DCLHb), a cell-free hemoglobin derived from human erythrocytes, on blood flow distribution and tissue oxygen extraction capabilities in endotoxic shock. Eighteen pentobarbital sodium-anesthetized, mechanically ventilated dogs received 2 mg/kg of E. coli endotoxin, followed by saline resuscitation to restore cardiac filling pressures to baseline levels. The animals were randomly divided into three groups: six served as control, six received DCLHb at a dose of 500 mg/kg (group 1) and six DCLHb at a dose of 1,000 mg/kg (group 2). Cardiac tamponade was then induced by saline injection in the pericardial sac to progressively reduce cardiac index and thereby allow study of tissue oxygen extraction capabilities. DCLHb had a dose-dependent vasopressor effect but did not significantly alter cardiac index or regional blood flow. During cardiac tamponade, critical oxygen delivery was 12.8 ± 0.7 ml · kg¹ · min¹ in the control group, but 8.6 ± 0.9 and 8.2 ± 0.7 ml · kg¹ · min¹ in groups 1 and 2, respectively (both P < 0.05 vs. control group). The critical oxygen extraction ratio was 39.1 ± 3.1% in the control group but 58.7 ± 12.8% and 60.2 ± 9.0% in groups 1 and 2, respectively. We conclude that DCLHb can improve whole body oxygen extraction capabilities during endotoxic shock in dogs.