For over four decades, pump flow rate during cardiopulmonary bypass (CPB) has been estimated using body surface area (BSA). As patients presenting for heart surgery are increasingly obese, this approach may no longer be appropriate and other estimates of systemic metabolism should be used, such as body mass index and lean body mass. Mixed venous oxygen saturation (SvO2) is a robust and independent estimate of the global efficacy of CPB. The aim of this study was to determine which factors, including body surface area, body mass index and lean body mass, best predict SvO2 during CPB. Forty-eight patients undergoing elective cardiac surgery requiring CPB were studied. Patients’ height, weight and skinfold thickness at four sites (biceps, triceps, subscapularis and suprailiac) were measured. Body surface area, lean body mass and body mass index were then calculated. Pump flow rate was maintained at 2.4 L/min/ m2 during CPB as per standard unit protocol. Arterial and mixed venous blood samples were taken during the cooling, stable hypothermia and rewarming phases of CPB. Nasopharyngeal temperatures and flow rates were recorded contemporaneously. The blood samples were analysed for oxygen saturation, haemoglobin concentration and partial pressures of oxygen and carbon dioxide. The values of the three time points were meaned. All potential predictor variables were then univariately correlated with mixed venous oxygen saturation (SvO2). Those correlating significantly (p < 0.1) were entered into a multivariate linear regression model. Nasopharyngeal temperature (beta = 0.615, p < 0.001) and lean body mass (beta = 0.256, p < 0.028) were the only significant predictors of SvO2 (r2 = 0.433, p2 < 0.001). Pump flow rates maintained at 2.4 L/min/m2 throughout CPB results in relative over-perfusion during hypothermia. Lean body mass may be a more sensitive estimate of systemic metabolism and, therefore, may provide a more accurate means of determining pump flow rate than body surface area in patients undergoing heart surgery.