Central venous oxygen saturation (ScvO₂) and mixed venous oxygen saturation (SvO₂) are widely used markers of tissue perfusion. Their role in cardiac surgery remains uncertain. This study conducted a systematic review and meta-analysis to evaluate the prognostic significance of ScvO₂ or SvO₂ in this setting. PubMed, Embase, and the Cochrane Library were searched from inception to March 31, 2025. Included studies enrolled adult or pediatric cardiac surgery patients reporting associations between ScvO₂ and/or SvO₂ values and clinical outcomes. Exclusion criteria were noncardiac surgery populations, case reports, editorials, and studies without outcome data. Quantitative synthesis was performed for studies reporting mortality data across different ScvO₂ or SvO₂ strata. Of 11,037 records screened, 29 studies (38,217 patients) were included in the qualitative synthesis and 9 studies in the meta-analysis. Most were observational, with heterogeneous measurement timing and thresholds. In particular, most studies performed measurement at a single time point. Low ScvO₂ or SvO₂ (<60%-65%) was significantly associated with increased mortality compared with normal values (risk ratio, 5.23; 95% confidence interval, 2.82-9.69; p < 0.00001; I² = 79%). No significant difference was observed between normal and supranormal (>77.4%-80%) values. Risk of bias was generally low to moderate, with confounding the main concern. Low ScvO₂ or SvO₂ identified patients at higher risk after cardiac surgery. However, most data were derived from single-time-point observational studies, and evidence regarding trends, repeated measurements, or study-defined high or supranormal values is limited.