We aimed to investigate whether normoxic cardiopulmonary bypass would limit myocardial oxidative stress in adults undergoing coronary artery bypass grafting. Patients scheduled to undergo elective isolated on-pump coronary artery bypass grafting were randomized to normoxia and hyperoxia groups. The normoxia group received 35% oxygen during anesthetic induction, 35% during hypothermic bypass, and 45% during rewarming. The hyperoxia group received 70%, 50%, and 70% oxygen, respectively. Coronary sinus blood samples were taken prior to initiation of cardiopulmonary bypass and after reperfusion for myocardial total oxidant and antioxidant status measurements. The primary endpoint was myocardial total oxidant status. Secondary endpoints were myocardial total antioxidant status and length of intensive care unit and hospital stay. Forty-eight patients were included. Twenty-two received normoxic management. Mean ± standard deviation of age was 58 ± 9.07 years. Groups were balanced in terms of demographics, risk factors, and operative data. Myocardial total oxidant status was significantly lower in the normoxia group following reperfusion (p = 0.03). There was no statistically significant difference regarding myocardial total antioxidant status and length of intensive care unit and hospital stay (p = 0.08, p = 0.82, and p = 0.54, respectively). Normoxic cardiopulmonary bypass is associated with reduced myocardial oxidative stress compared to hyperoxic cardiopulmonary bypass in adult coronary artery bypass patients.