Objective: The aim of this study was to determine whether the increase in post-operative oxygen consumption (ΔVO2) in cardiac surgery patients is related to endotoxemia and subsequent cytokine release and whether ΔVO2 can be used as a parameter of post-perfusion syndrome. Design: Prospective study. Setting: Operating room and intensive care unit of a university hospital. Patients: Twenty-one consecutive male patients undergoing elective coronary artery bypass surgery without major organ dysfunction and not receiving corticosteroids. Measurements and results: Plasma levels of endotoxin, tumor necrosis factor (TNF) and interleukin-6 (IL-6) were measured before, during and for 18 h after cardiac surgery. Oxygen consumption, haemodynamics, the use of IV fluids and dopamine, body temperature and the time of extubation were also measured. Measurements from patients with high ΔVO2 (≥ median value of the entire group) were compared with measurements from patients with low ΔVO2 (< median). Patients with high ΔVO2 had higher levels of circulating endotoxin (P = 0.004), TNF (P = 0.04) and IL-6 (P = 0.009) received more IV fluids and dopamine while in the ICU, and were extubated later than patients with low ΔVO2. Several hours after ΔVO2 the patient's body temperature rose. Forward stepwise regression analysis showed that circulating endotoxin and TNF explained 50% of the variability of ΔVO2. Conclusions: This study demonstrates that patients with high post operative oxygen consumption after elective cardiac surgery have higher circulating levels of endotoxin, TNF and IL-6 and also have more symptoms of post-perfusion syndrome. Early detection of high VO2 might be used as a clinical signal to improve circulation in order to meet the high oxygen demand of inflammation. In addition, continuous measurement of VO2 provides us with a clinical parameter of inflammation in interventional studies aiming at a reduction of endotoxemia or circulating cytokines.