Introduction: Diabetes mellitus (DM) is one of the well-known risk factors of postoperative stroke in cardiac surgery. Cerebrovascular CO2 reactivity and the changes in cerebral blood flow are impaired in diabetic patients. Regional cerebral oxygen saturation (rSO2) measured using near-infrared spectroscopy (NIRS) has been utilized in cardiac surgery to evaluate cerebral oxygenation. However, the difference of the rSO2 values between diabetic and non-diabetic patients during cardiopulmonary bypass (CPB) has not been well investigated. The aim of this study was to compare the rSO2values of diabetic and non-diabetic patients who underwent cardiac surgery. Methods: Thirty diabetic patients (DM group) and 30 age- and gender-matched non-diabetic patients (NDM [control] group) who underwent coronary artery bypass grafting (CABG), valve surgery, or both utilizing normothermic CPB were retrospectively investigated. The mean values of rSO2 at nine time points during the entire period of cardiac surgery were measured. Results: The rSO2 values in the DM group were significantly lower than those in the NDM group (p < 0.01) and the difference between the groups increased with the time after the initiation of CPB. Conclusions: The rSO2 values in diabetic patients are lower than those in non-diabetic patients during cardiac surgery with normothermic CPB. A further large prospective study will be needed to investigate the relationship between lower rSO2 values in diabetic patients and postoperative outcomes as well as the mechanism of the lower values.