Objectives: Elevated soluble urokinase-type plasminogen activator receptor (suPAR) and high-sensitivity C-reactive protein (hsCRP) have been associated with increased mortality in patients with cardiovascular disease. The aim of the present study was to explore the relationship between suPAR and hsCRP values and associated mortality after elective cardiac surgery. A secondary aim was to assess whether a combined risk model of European System for Cardiac Operative Risk Evaluation (EuroSCORE II), suPAR, and/or hsCRP would improve the prognostic accuracy compared with EuroSCORE II alone. Design: Retrospective observational study. Setting: Single-center, university hospital. Participants: Adult patients admitted for elective on-pump cardiac surgery were included. Biobank blood samples were obtained from previous research projects at a tertiary heart center from 2012 to 2018. Interventions: None. Measurements and Main Results: A total of 931 patients were included. Kaplan-Meier and Cox proportional hazard analyses were used to explore a potential association between preoperative suPAR and hsCRP values and all-cause mortality up to one year after surgery. Thirty-day mortality was predicted from suPAR, hsCRP, and EuroSCORE II by logistic regression and compared using area under the receiver operating characteristics curve and Brier scores. After adjustment for known confounders, a doubling of suPAR and hsCRP corresponded to a hazard ratio for all-cause mortality of 2.27 (95% confidence interval 1.65-3.11; p < 0.001) and 1.26 (95% confidence interval 1.07-1.49; p = 0.005), respectively. However, adding the biomarkers to EuroSCORE II did not improve prediction/discrimination with respect to 30-day mortality. Conclusions: Elevated preoperative levels of suPAR and hsCRP were associated with all-cause mortality in elective cardiac surgery patients. However, inclusion of biomarkers did not improve the prognostic accuracy of EuroSCORE II.