One of the strongest risk factors for death in individuals undergoing cardiac surgery is Cardiac Surgery Associated-Acute Kidney Injury (CSA-AKI). Although the minimum kidney oxygen delivery index (DO₂i) during cardiopulmonary bypass (CPB) has been reported, the optimal threshold value has not yet been established. A prospective study was conducted from June 2012 to January 2016 to asses how DO₂i influences the pathogenesis of CSA-AKI, as well as its most favorable cut-off value. DO₂ levels were recorded at the beginning, middle, and end of the CPB. The association between DO₂i and CSA-AKI was investigated using multivariable logistic regression analysis. The optimal cut-off of DO₂i as a predictor of CSA-AKI was determined using Classification and Regression Tree (CART) analysis. A total of 782 consecutive patients were enrolled. Of these, 231 (29.5%) patients developed AKI. Optimal DO₂i thresholds of 303 mL/min/m² during the CPB and 295 mL/min/m² at the end of the intervention were identified, which increased the odds of CSA-AKI almost two-fold (Odds Ratio (OR), 1.90; 95% CI, 1.12–3.24) during the surgery and maintained that risk (OR 1.94; 95% CI, 1.15–3.29) until the end. Low DO₂i during cardiopulmonary bypass is a risk factor for CSA-AKI that cannot be ruled out. Continuous renal oxygen supply monitoring for adult patients could be a promising method for predicting AKI during CPB.