Aim: To assess the association with outcomes of cardiac index (CI) and mixed venous oxygen saturation (SvO2) in comatose patients resuscitated from out-of-hospital cardiac arrest (OHCA). Methods: In the cohort study of 789 patients included in the “BOX”-trial, 565 (77%) patients were included in this hemodynamic substudy (age 62 ± 13 years, male sex 81%). Pulmonary artery catheters were inserted shortly after ICU admission. CI and SvO2 were measured as soon as possible in the ICU and until awakening or death. The endpoints were all-cause mortality at 1 year and renal failure defined as need for renal replacement therapy. Results: First measured CI was median 1.7 (1.4–2.1) l/min/m², and first measured SvO2 was median 67 (61–73) %. CI < median with SvO2 > median was present in 222 (39%), and low SvO2 with CI < median was present in 59 (11%). Spline analysis indicated that SvO2 value < 55% was associated with poor outcome. Low CI at admission was not significantly associated with mortality in multivariable analysis (p = 0.14). SvO2 was significantly inversely associated with mortality (hazard ratio_adjusted: 0.91 (0.84–0.98) per 5% increase in SvO2, p = 0.01). SvO2 was significantly inversely associated with renal failure after adjusting for confounders (OR_adjusted: 0.73 [0.62–0.86] per 5% increase in SvO2, p = 0.001). The combination of lower CI and lower SvO2 was associated with higher risk of mortality (hazard ratio_adjusted: 1.54 (1.06–2.23) and renal failure (OR_adjusted: 5.87 [2.34–14.73]. Conclusion: First measured SvO2 after resuscitation from OHCA was inversely associated with mortality and renal failure. If SvO2 and CI were below median, the risk of poor outcomes increased significantly. Registration: The BOX-trial is registered at clinicaltrials.gov (NCT03141099, date 2017–30–04, retrospectively registered). Graphical abstract: [Figure not available: see fulltext.].