The brain has high oxygen extraction, thus the regional cerebral tissue oxygen saturation (rSO₂) is lower than the central venous oxygen saturation (ScvO₂). We hypothesised that diabetes widens the physiological saturation gap between ScvO₂ and rSO₂ (gSO₂), and the width of this gap may vary during various phases of cardiac surgery. Cardiac surgery patients with (n = 48) and without (n = 91) type 2 diabetes mellitus (T2DM) underwent either off-pump coronary artery bypass (OPCAB) or other cardiac surgery necessitating cardiopulmonary bypass (CPB) were enrolled. rSO₂ was measured by near-infrared spectroscopy (NIRS) and ScvO₂ was determined simultaneously from central venous blood. rSO₂ was registered before and after anaesthesia induction and at different stages of the surgery. ScvO₂ did not differ between the T2DM and control patients at any stage of surgery, whereas rSO₂ was lower in T2DM patients, compared to the control group before anaesthesia induction (60.4 ± 8.1%[SD] vs. 67.2 ± 7.9%, p<0.05), and this difference was maintained throughout the surgery. After anaesthesia induction, the gSO₂ was higher in diabetic patients undergoing CPB (20.2 ± 10.4% vs. 12.4 ± 8.6%, p < 0.05) and OPCAB grafting surgeries (17.0 ± 7.5% vs. 9.5 ± 7.8%, p < 0.05). While gSO₂ increased at the beginning of CPB in T2DM and control patients, no significant intraoperative changes were observed during the OPCAB surgery. The wide gap between ScvO₂ and rSO₂ and their uncoupled relationship in patients with diabetes indicate that disturbances in the cortical oxygen saturation cannot be predicted from the global clinical parameter, the ScvO₂. Thus, our findings advocate the monitoring value of NIRS in T2DM.