Sixteen patients undergoing hypothermic cardiopulmonary bypass for open heart surgery were studied prospectively. Oxygen consumption and CO2 production showed a marked increase during the first 6 h postoperatively. Consequently, the measured resting energy expenditure was markedly elevated compared to the predicted energy expenditure. This hypermetabolic response occurred simultaneously with maximum spontaneous rewarming after the end of surgical procedures. Ventricular function was low throughout the postoperative period, and no cardiac response to increased energy requirements was recorded. On the contrary, marked increases in arteriovenous oxygen and CO2 difference were observed during the period of highest resting energy expenditure. We conclude that the first hours after hypothermic cardiopulmonary bypass represent the period of highest risk for decompensation. The continuous monitoring of CO2 production is suggested as a useful clinical method to detect postoperative changes in metabolic rate.