Background: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies. Methods: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs). Results: Twenty-nine animal studies, including 1,266 animals, were identified. None of the studies were judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22–0.38, P