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Abstract Background: Cardiac surgery can produce persistent deficit in the ratio of Oxygen Delivery (DO2) to Oxygen Consumption (VO2). Central venous oxygen Saturation (ScvO2) is an accessible and indirect measure of DO2/VO2 ratio. Objective: To monitor perioperative ScvO2 and assess its correlation with mortality during cardiac surgery. Methods: This prospective observational study evaluated 273 patients undergoing cardiac surgery. Blood gas samples were collected to measure ScvO2 at three time points: T0 (after anesthetic induction), T1 (end of surgery), and T2 (24 hours after surgery). The patients were divided into two groups (survivors and nonsurvivors). The following outcomes were analyzed: intrahospital mortality, length of Intensive Care Unit (ICU) and hospital stay (LOS), and variation in ScvO2. Results: Of the 273 patients, 251 (92%) survived and 22 (8%) did not. There was a significant perioperative reduction of ScvO2 in both survivors (T0 = 78% ± 8.1%, T1 = 75.4% ± 7.5%, and T2 = 68.5% ± 9%; p< 0.001) and nonsurvivors (T0 = 74.4% ± 8.7%, T1 = 75.4% ± 7.7%, and T2 = 66.7% ± 13.1%; p < 0.001). At T0, the percentage of patients with ScvO2< 70% was greater in the nonsurvivor group (31.8% vs. 13.1%; p= 0.046) and the multiple logistic regression showed that ScvO2 is an independent risk factor associated with death, OR = 2.94 (95% CI 1.10−7.89) (p= 0.032). The length of ICU and LOS were 3.6 ± 3.1 and 7.4 ± 6.0 days respectively and was not significantly associated with ScvO2. Conclusions: Early intraoperative ScvO2 < 70% indicated a higher risk of death. A perioperative reduction of ScvO2 was observed in patients undergoing cardiac surgery, with high intraoperative and lower postoperative levels.