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Abstract Background Alactic base excess (ABE) is a novel biomarker that estimates the renal capability of handling acid–base alterations during the sepsis. Hence, the aim of this study was to evaluate the use of ABE to predict the renal replacement therapy (RRT) in patients with septic shock. Methods A total of 164 patients admitted to the intensive care units with a diagnosis of septic shock according to the third international consensus on sepsis and septic shock (Sepsis-3) were included. This study was retrospective, single center, and conducted between January 1, 2016, and December 31, 2020. The individuals were stratified in patients who did [n = 68] or did not [n = 96] receive the RRT. The diagnostic performed of the variables for the classification into patients who required RRT was evaluated by receiver operating characteristic (ROC) analysis and area under curve (AUC) was calculated. Univariate and multivariate logistic regression models were used to identify risk factors for RRT. Results The median age of the patients was 59 years and female sex (51.8%) predominated. ABE (odds ratio [OR] 1.2270, [95% confidence interval [CI] 1.0453–1.4403], p = 0.0124) and urea (OR 1.0114, [95% CI 1.0053–1.0176], p = 0.0002) were associated with risk of RRT. HCO3− (OR 0.6967, [95% CI 0.5771–0.8410], p = 0.0002) was a protective factor of RRT. ABE (AUC = 0.649, p 75 mg/dL, respectively. Conclusion Although HCO3− is associated with low risk, ABE and urea are independent risk factors for RRT in the patients with septic shock.