The effect of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) on the mortality of patients with sepsis is not well characterized.To elucidate the association between prior ACEI or ARB exposure and mortality in sepsis.The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all studies of premorbid ACEI or ARB use and sepsis mortality until November 30 2019. Two reviewers independently assessed, selected, and abstracted data from studies reporting ACEIs or ARBs, sepsis, and mortality. The primary extracted data consisted of premorbid ACEI or ARB exposure, mortality, and general patient data. Two reviewers independently assessed the risk of bias and quality of evidence.A total of six studies comprising 281238 patients with sepsis, including 49799 cases with premorbid ACEI or ARB exposure were eligible for analysis. Premorbid ACEIs or ARBs exposure decreased the 30-d mortality in patients with sepsis. Moreover, the use of ACEIs or ARBs was associated with approximately a 6% decreased risk of 30-d mortality.The results of this systematic review suggest that ACEI or ARB exposure prior to sepsis may be associated with reduced mortality. Further high-quality cohort studies and molecular mechanism experiments are required to confirm our results.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.