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Central venous oxygen saturation (ScvO2) is a valuable prognostic marker in sepsis. However, its value in cardiac surgery has not been assessed yet. This study aimed at evaluating ScvO2 as a tool for predicting short-term organ dysfunction (OD) after cardiac surgery.A prospective cohort including cardiac surgery patients submitted to a goal-oriented therapy to maintain ScvO2 above 70% was studied. Postoperative blood samples collected at 30 minutes (T1), 6 hours (T2), and 24 hours (T3) for ScvO2 measurement were selected to further analysis. Two groups were formed according to the absence (G0) or presence (G1) of OD defined as a Sequential Organ Failure Assessment (SOFA) score ≥5 on the third postoperative day. A logistic regression analysis was performed to identify the variables independently associated with OD on the third postoperative day.From the 246 patients included, 54 (22%) developed OD and were defined as G1. The mortality rates in G0 and G1 were 1.6% and 31.5%, respectively (P < .001). In the comparative analysis between G0 and G1, the ScvO2 values were remarkably lower in G1 at T1 (66.2 ± 9.2 vs 62.3 ± 11.6; P = .009), T2 (69.6 ± 5.9 vs 63.5 ± 9.4; P ≤ .001), and T3 (69.6 ± 5.6 vs 64.6 ± 6.4; P ≤ .001). The variables independently associated with OD in the final logistic regression model were Cleveland score (95% CI: 1.13–1.44; OR: 1.27; P < .001), lactate at T3 (95% CI:1.21–3.15; OR 1.95; P = .006), BE at T3 (95% CI:0.69–0.93; OR 0.80; P = .005); ScvO2 at T2 (95% CI:0.86–0.96; OR 0.91; P = .002), and ScvO2 at T3 (95% CI:0.83–0.95; OR 0.89; P = .002).Postoperative ScvO2 can be a valuable tool to predict OD after major cardiac surgeries. Its kinetics should be carefully followed in that setting.