It is unclear if premorbid use of beta-blockers affects sepsis outcomes. The present systematic review aimed to assess the impact of premorbid beta-blocker use on mortality and the need for mechanical ventilation in patients with sepsis. Embase, Scopus, PubMed and Web of Science were searched for studies comparing outcomes of patients with sepsis based on the premorbid use of beta-blockers. The primary outcome was mortality, and the secondary outcome was the need for mechanical ventilation. The results were reported as odds ratios (ORs) with 95% confidence intervals (CIs). A total of 17 studies including 64,586 patients with sepsis were included. Of them, 8,665 patients received premorbid beta-blockers and 55,921 patients were not treated with premorbid beta-blockers and served as a control group. Pooled analysis of mortality rates revealed that premorbid use of beta-blockers did not affect in-hospital mortality (OR: 0.96; 95% CI: 0.78, 1.18; and I 2 =63%) but significantly reduced one-month mortality rates (OR: 0.83; 95% CI: 0.72, 0.96; and I 2 =63%). Combined analysis of adjusted data showed that premorbid beta-blockers were associated with a significant survival advantage in patients with sepsis (OR: 0.81; 95% CI: 0.72, 0.92; and I 2 =70%). However, there was no effect of premorbid use of beta-blockers on the need for mechanical ventilation (OR: 0.93; 95% CI: 0.66, 1.30); and I 2 =72%). The results of the present study indicated that premorbid use of beta-blockers is associated with improved survival in patients with sepsis. However, it does not impact the need for mechanical ventilation. The results should be interpreted with caution as the data is observational and unadjusted.