The effects of diaspirin crosslinked hemoglobin (DCLHb, Baxter Health Care Corp., Round Lake, IL) on oxygen exchange in the setting of cardiopulmonary bypass (CPB) are unknown. Six calves (71.2 +/- 1.3 kg) were connected to CPB by jugular venous and carotid arterial cannulation for 5 hours. Each 1 hour period included 45 min of partial CPB (mean flow rate of 50 ml/kg per min) followed by 15 min without CPB, at the end of which 500 ml of blood were substituted for with either 500 ml of hydroxyethyl starch (Haes; n = 3) or 500 ml of DCLHb (n = 3). A total of 2 liters of blood was, thus, exchanged (28 ml/kg of blood substitute). Values are expressed as mean +/- 1 SD. Analysis of variance for repeated measurements was used. The cardiac output (CO) values at 1 h, 3 h, and 5 h were in the Haes group: 5.7 +/- 2, 6.7 +/- 2.5, and 7.7 +/- 2.5L/min, and in the DCLHb group: 5.7 +/- 0.6, 4 +/- 1, and 4.7 +/- 1.2 L/min, respectively. The arteriovenous oxygen content difference (Ca-Cvo2) values at 1 h, 3 h, and 5 h were in the Haes group: 4.6 +/- 1, 3.3 +/- 1.5, and 3.5 +/- 1.5 ml/dl, and in the DCLHb group: 4.9 +/- 0.6, 7.4 +/- 0.7, and 6.6 +/- 0.6 ml/dl, respectively. The oxygen consumption (Vo2) values at 1 h, 3 h, and 5 h were in the Haes group: 244 +/- 29, 198 +/- 58, and 249 +/- 42 ml/min, and in the DCLHb group: 273 +/- 28, 296 +/- 75, and 306 +/- 65 ml/min, respectively. CO and Ca-Cvo2 showed a significant difference (p < 0.01), whereas Vo2 did not (p = 0.52). In the DCLHb group of this CPB animal model, the cardiac output is lower and the arteriovenous oxygen content difference higher than in the Haes group, allowing for preserved oxygen consumption.