BackgroundSepsis presents a significant healthcare challenge, characterized by high morbidity and mortality rates. There is a scarcity of relevant studies investigating the association between serum lactate dehydrogenase level and the prognosis of sepsis in patients from intensive care unit, with smaller sample sizes compared to other studies.MethodsA retrospective analysis was conducted utilizing data from the Second Affiliated Hospital of Guangzhou Medical University and the Medical Information Mart for Intensive Care IV (MIMIC-IV). The primary outcome was the in-hospital mortality. Multivariate Cox proportional hazards regression was adopted to assess the independent association. Receiver operator characteristic (ROC) curve was used to evaluate the predictive value.ResultsWe included a total of 2148 patients in the Guangzhou Sepsis Cohort (GZSC) database and 5830 patients in the MIMIC-IV database. In multivariate Cox proportional hazards regression, high levels of LDH are significantly associated with higher mortality (HR = 1.21, 95% CI 1.13–1.30, p < 0.001 in the GZSC database and HR = 1.19, 95% CI 1.13–1.25, p < 0.001 in the MIMIC-IV database). The ROC curves showed that the AUC of LDH was 0.663 in the GZSC database and 0.660 in the MIMIC-IV database.ConclusionsA lower lactate dehydrogenase level is associated with reduced in-hospital mortality among patients with sepsis, suggesting its potential as a valuable marker for predicting prognosis in this patient population.