Objectives: The aim of this study was to investigate the potential of preoperative neopterin levels as a predictive marker for postoperative acute kidney injury (AKI) in patients undergoing on-pump cardiac surgery, in addition to other potential risk factors. Methods: This observational study included 91 patients who underwent elective cardiac surgery under cardiopulmonary bypass. Of these, 35 patients (38.46 %) experienced AKI following surgery, as outlined by the Kidney Disease Improving Global Outcomes (KDIGO) standards. The study participants were divided into two groups depending on whether they had developed AKI after the surgery or not. The study compared two groups and utilized logistic regression analysis to evaluate potential predictors. A receiver operating characteristic (ROC) analysis was conducted to determine the ability of preoperative neopterin levels to predict the occurrence of AKI. Results: A comparison of the baseline demographic, clinical, laboratory, and echocardiographic characteristics was conducted between patients who suffered from AKI and those who did not. The multivariate analysis demonstrated that EuroSCORE II (OR, 4.525; 95 % CI, 1.29-15.87; p=0.019), X-clamp time (OR, 1.157; 95% CI, 1.01-1.326; p=0.035), and neopterin levels (OR, 22.952; 95 % CI, 3.14-167.763; p=0.002) were independently predicted the post-cardiac surgery AKI. ROC analysis identified a cut-off value of 9.65 nmol/L, which had a sensitivity of 91.4 % and a specificity of 91.1 % (area under the curve, 0.98; 95 % CI, 0.958-1; p<0.001). Conclusions: Our study emphasizes the potential of preoperative neopterin levels, EuroSCORE II, and X-clamp time as independent predictors of postoperative AKI, even in milder cases, in individuals undergoing on-pump cardiac surgery.