The relative contributions of oxygen delivery (DO2) and oxygen extraction (O2ER) to the increase in cellular oxygen uptake (V̇O2) after cardiopulmonary bypass were studied prospectively in 36 patients after coronary artery bypass grafting (n = 18), valve replacement (n = 17), and removal of a left atrial tumor (n = 1). V̇O2 was calculated from the Fick equation and DO2 from ther-modilution cardiac output and arterial oxygen content. During the first 24 h after cardiac surgery, there was a strong relation between V̇O2 and DO2 (V̇O2 = 28 + 0.27 × DO2, r = 0.79, P < 0.0001) but not between V̇O2 and oxygen extraction. Mixed venous oxygen saturation (SJOURNAL/asag/04.02/00000539-199312000-00004/ENTITY_OV0456/v/2017-07-21T015502Z/r/image-pngO2) was usually reduced when cardiac index was below 2.0 L·min−1·m−2. Patients with a prolonged intensive care unit course (>24 h) had lower cardiac index and lower SJOURNAL/asag/04.02/00000539-199312000-00004/ENTITY_OV0456/v/2017-07-21T015502Z/r/image-pngO2 than the other patients. Therefore, the progressive increase in V̇O2 after cardiac surgery is accomplished primarily by an increase in cardiac output and DO2. It is usually when cardiac function is compromised that O2ER increases and SJOURNAL/asag/04.02/00000539-199312000-00004/ENTITY_OV0456/v/2017-07-21T015502Z/r/image-pngO2 decreases.