Objective To explore the application of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) for patients with sepsis and hyperlactacidemia, and to provide a basis for the clinical application of RCA in such patients. Methods Sepsis patients who underwent RCA-CRRT at West China Hospital of Sichuan University between May 2021 and May 2023 were retrospectively included. Patients were divided into a normal lactate group (≤2.0 mmol/L) and a hyperlactacidemia group (>2.0 mmol/L) based on their initial lactate levels before CRRT, and subgroup analysis was performed on patients with moderate hyperlactacidemia (2 mmol/L<lactate level<4 mmol/L) and severe hyperlactacidemia (≥4.0 mmol/L). Propensity score matching (PSM) was used, and baseline characteristics and outcome measures of different groups of patients were compared. Results A total of 441 patients were included, with 228 in the normal lactate group and 213 in the hyperlactacidemia group. Before PSM, there were statistically significant differences in the proportion of liver failure, proportion of chronic kidney disease, mean arterial pressure, bicarbonate, total bilirubin, creatinine, activated partial thromboplastin time, international standardized ratio, procalcitonin, and interleukin-6 between the normal lactate group and the hyperlactacidemia group (P<0.05). After PSM, there were 162 patients in both the normal lactate group and the hyperlactacidemia group. There was no statistically significant difference in baseline characteristics between the two groups of patients (P>0.05). The incidence of citric acid accumulation in the normal lactate group and the hyperlactacidemia group was 13.0% and 25.9%, respectively (P<0.05). There was no statistically significant difference in the incidence of metabolic acidosis, metabolic alkalosis, hypernatremia, filter coagulation events, or in-hospital mortality between the two groups (P>0.05). Kaplan-Meier survival analysis showed that there was no statistically significant difference in the first extracorporeal circulation lifespan between the normal lactate group and the hyperlactacidemia group (P>0.05). Among 213 patients with hyperlactacidemia, 186 had moderate hyperlactacidemia and 27 had severe hyperlactacidemia. Before PSM, there were statistically significant differences in the proportion of male, proportion of diabetes, albumin level, international standardized ratio, and interleukin-6 between moderate and severe hyperlactacidemia groups (P<0.05). After PSM, there were 22 patients in both the moderate and severe hyperlactacidemia groups. There was no statistically significant difference in baseline characteristics between the two groups of patients (P>0.05). The incidence of citric acid accumulation was 18.2% and 50.0% in the moderate and severe hyperlactacidemia groups, respectively (P<0.05). There was no statistically significant difference in the incidence of metabolic acidosis, metabolic alkalosis, hypernatremia, filter coagulation events, or in-hospital mortality between the two groups (P>0.05). Kaplan-Meier survival analysis showed that there was no statistically significant difference in the first extracorporeal circulation lifespan between the moderate and severe hyperlactacidemia groups (P>0.05). Conclusion When RCA is used for CRRT anticoagulation in patients with sepsis and hyperlactacidemia, the incidence of citric acid accumulation is high (especially in patients with severe hyperlactacidemia), and should be closely monitored.