Objectives: To determine the relationship between serum levels of oxidative stress (OS) parameters and regional cerebral oxygen saturation (rSO2), as well as postoperative clinical outcomes in patients undergoing coronary artery bypass graft surgery (CABG). Materials and Methods: This prospective observational study included 64 adult patients undergoing elective CABG [on-pump-CABG (n=48) and off-pump CABG (n=16)]. The OS level was determined according to total oxidant status and malondialdehyde. OS levels and rSO2 values were measured intraoperatively at three-time points (T1: after induction, T2: 15min before aortic cross-clamp removal or before the last distal anastomosis, T3: 15min after aortic cross-clamp removal or the last distal anastomosis). Results: In the on-pump group, OS levels at T2-3 and lactate values at T2-3 were found to be higher (p=<0.001), rSO2 at T2 was lower (p=0.024). There was a negative correlation between rSO2-T2 values and OS parameters, lactate levels at T2-3, aortic clamp time, postoperative mechanical ventilation (MV) time, and length of stay (LOS) in the ICU. In the multivariate linear regression analysis [F(2.61)=8.26, p=0.001], lactate values at T2 were found to be the only factor affecting the OSI-T2 index (Beta=0.388, p=0.006). Conclusıons: In this study, we observed that OS levels were increased and rSO2 values were relatively low during on-pump CABG procedures, furthermore, lower rSO2 values were associated with increased OS levels and poor postoperative clinical outcomes. The OS response and cerebral oxygenation could be improved in off-pump CABG by limiting global ischemia, resulting in a favourable postoperative outcomes such as less MV time and LOS in the ICU.