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Background Normal saline is commonly used for resuscitation in sepsis patients but has a high chloride content, potentially increasing the risk of acute kidney injury (AKI). This study evaluated risk factors and developed a predictive risk score for AKI in sepsis patients treated with normal saline. Methods This retrospective cohort study utilized the medical and electronic health records of sepsis patients who received normal saline between January 2018 and May 2020. Predictors of AKI used to construct the predictive risk score were identified through multivariate logistic regression models, with discrimination and calibration assessed using the area under the receiver operating characteristic curve (AUROC) and the expected-to-observed (E/O) ratio. Internal validation was conducted using bootstrapping techniques. Results AKI was reported in 211 of 735 patients (28.7%). Eight potential risk factors, including norepinephrine, the Acute Physiology and Chronic Health Evaluation II score, serum chloride, respiratory failure with invasive mechanical ventilation, nephrotoxic antimicrobial drug use, history of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use, history of liver disease, and serum creatinine were used to create the NACl RENAL-Cr score. The model demonstrated good discrimination and calibration (AUROC, 0.79; E/O, 1). The optimal cutoff was 2.5 points, with corresponding sensitivity, specificity, positive predictive value, and negative predictive value scores of 71.6%, 72.5%, 51.2%, and 86.4%, respectively. Conclusions The NACl RENAL-Cr score, consisting of eight critical variables, was used to predict AKI in sepsis patients who received normal saline. This tool can assist healthcare professionals when deciding on sepsis treatment and AKI monitoring.