Abstract Background Outcome prediction for patients with sepsis may be conductive to early aggressive interventions. Numerous biomarkers and multiple scoring systems have been utilized in predicting outcomes, however, these tools were either expensive or inconvenient. We performed a meta-analysis to evaluate the prognostic role of red blood cell distribution width (RDW) in patients with sepsis. Methods The online databases of Embase, Web of science, Pubmed, Corchrane library, Chinese Wanfang database, CNKI database were systematically searched from the inception dates to June, 24th, 2020, using the keywords red cell distribution width and sepsis. The odds ratio (OR) or Hazards ratio (HR) with corresponding 95% confidence intervals (95%CI) were pooled to evaluate the association between baseline RDW and sepsis. A random-effects model was used to pool the data, and statistical heterogeneity between studies was evaluated using the I 2 statistic. Sensitivity and subgroup analyses were performed to detect the publication bias and origin of heterogeneity. Results Eleven studies with 17,961 patients with sepsis were included in the meta-analysis. The pooled analyses indicated that increased baseline RDW was associated with mortality (HR = 1.14, 95%CI 1.09–1.20, Z = 5.78, P < 0.001) with significant heterogeneity (I 2 = 80%, P heterogeneity < 0.001). Similar results were found in the subgroup analysis stratified by site of infection, comorbidity, Newcastle-Ottawa Scale (NOS) score, study design, patients’ country. The predefined subgroup analysis showed that NOS score may be the origin of heterogeneity. Conclusions For patients with sepsis, baseline RDW may be a useful predictor of mortality, patients with increased RDW are more likely to have higher mortality.