Cardiac surgery-associated acute kidney injury (CS-AKI) is common in infants and is associated with negative outcomes. Nadir indexed oxygen delivery (DO2i) during cardiopulmonary bypass (CPB) is associated with the occurrence of postoperative CS-AKI, with critical thresholds for DO2i reported to be 262 to 300 mL/min/m2 in adults. However, given that infants have a higher metabolic rate and oxygen demand, the critical DO2i in infants is not comparable with existing adult standards. This study aimed to explore the critical DO2i threshold during pediatric CPB. Between March 2019 and April 2020, 106 consecutive infants undergoing cardiac surgery with CPB were admitted to this prospective observational cohort study. The DO2i levels of each patient were monitored during CPB. Pre- and intraoperative factors were tested for independent association with CS-AKI. The postoperative outcomes of patients with or without CS-AKI were compared. In our patient population (n = 83), we identified 25 patients (38.5%) with postoperative CS-AKI. Multivariate analysis revealed 2 independent risk factors for onset of CS-AKI: CPB duration and nadir DO2i. The lowest suitable DO2i during CPB in the present population was 353 mL/min/m2 (sensitivity, 65.6%; specificity, 74.5%). CS-AKI during pediatric CPB remained significantly associated with an increased morbidity, related mainly to a postoperative low cardiac output syndrome, but not to mortality. The lowest suitable DO2i during CPB in the infant population undergoing cardiac surgery was 353 mL/min/m2. Below this threshold, there was a high probability of inducing CS-AKI.