Background Acidosis during cardiopulmonary bypass (CPB) has been related to the strong ion difference (SID) and the composition of intravascular fluids that are administered. Less intravascular fluids tend to be administered during off- than on-pump CABG and should influence the degree of acidosis that develops. This study aimed to explore the role of CPB in the development of acidosis by comparing changes in hydrogen ion concentration ([H+]) and electrolytes in patients undergoing on- and off-pump coronary artery bypass graft (CABG) surgery. Methods Eighty two patients had arterial blood gas measurements pre-operatively, following CABG and at approximately 0600 h the morning after surgery. Carbon dioxide tension (PaCO2) and concentrations of sodium, potassium, chloride, [H+], bicarbonate and haemoglobin were measured and strong ion difference calculated. Data was analysed using mixed repeated-measures analysis of variance. Results Intra-operatively, mean SID decreased more in the on- compared to the off-pump group (4.0 mmol/L, 95% confidence interval 2.8-5.3 mmol/L, p