Objective: To determine whether intra-pulmonary oxygen consumption or whole body oxygen consumption is the main determinant of the hypermetabolic response after cardiopulmonary bypass. Secondly, which method of measuring oxygen consumption best quantifies this hyperdynamic response. Design: We measured oxygen consumption by analysing respiratory gas (VO2-gas), carbon dioxide excretion (VCO2), and respiratory exchange ratio (RER = VCO2/VO2), and calculated oxygen consumption using the Fick-method (VO2-Fick) and intra-pulmonary oxygen consumption (VO2-gas - VO2-Fick) in patients at fixed times before and after elective cardiac surgery. Next, comparisons were made between methods and also between measurements at different times before and after bypass. Setting: University hospital Patients: 10 elective cardiac surgical patients Interventions: None Measurements and results: VO2-gas, VCO2 and RER were measured with an open circuit indirect calorimeter VO2-Fick was calculated: VO2-Fick=cardiac indexx(arterial - mixed venous oxygen content). Intrapulmonary oxygen consumption was calculated as the difference between VO2-gas and VO2-Fick. Both VO2-gas and VO2-Fick were about 20% higher after bypass than after induction of anaesthesia. Absolute values of VO2-gas were about 30% higher than VO2-Fick. Intra-pulmonary oxygen consumption accounted for 32% of whole body oxygen consumption after induction of anaesthesia and did not increase after bypass. Conclusion: Whole body oxygen consumption and not intra-pulmonary oxygen consumption is the main determinant of the hypermetabolic response after bypass. Increased intra-pulmonary oxygen consumption is not related to bypass. VO2-gas best quantifies this hypermetabolic response directly after bypass, and not VO2-Fick, VCO2 or intra-pulmonary oxygen consumption, since VO2-Fick excludes intra-pulmonary oxygen consumption and VCO2 does not reflect metabolism directly after bypass.