ObjectivesCarboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery-associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. DesignA retrospective cohort study. SettingTertiary university-affiliated metropolitan hospital: single center. ParticipantsAdult on-pump cardiac surgery patients from July 2014 to June 2022 (n=1698). InterventionsNone. Measurements and Main ResultsPatients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariate logistic regression analysis, the highest quartile (CO-Hb ≥1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio=1.45 compared to the lowest quartile (CO-Hb<1.0%), 95% CI 1.023-2.071; p=0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 μmol/L, p<0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p<0.001) and AKI (p<0.001) on univariate analysis and shorter time to event for AKI or death (p<0.001). ConclusionsCO-Hb ≥1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and already available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention.