We planned a systemic review and meta-analysis to evaluate the diagnostic accuracy of Monocyte Distribution Width (MDW) in aiding the diagnosis of sepsis in the Emergency Department (ED) and Intensive Care Unit (ICU). A systematic literature search was performed in PubMed, Scopus, and OVID to retrieve studies published up to 29 January 2024. We examined results using mean difference and conducted a diagnostic test accuracy (DTA) meta-analysis using a bivariate random effects model. Pooled results showed that MDW was significantly higher in sepsis patients admitted to the ED (MD = 5.59, 95%CI: 4.14-7.05) or to the ICU (MD = 8.30, 95%CI: 2.98-13.62). Nine studies conducted in the ED were included in the DTA review. The overall sensitivity was 0.80 (95%CI: 0.75-0.85), the specificity was 0.76 (95%CI: 0.66-0.83), and the false-positive rate (FPR) was 0.24 (95%CI: 0.17-0.34). Three studies were conducted in the ICU, but only two were included in the DTA meta-analysis. Of the 662 patients admitted to the ICU, 175 developed sepsis, showing higher MDW values than non-septic patients. However, significant heterogeneity was noted among the studies. MDW is a helpful biomarker for sepsis in adult patients admitted to the ED and ICU. In the ED, MDW could aid clinicians in ruling out sepsis.