Aim: Syndecan-1 (SDC-1) has been shown to have a high predictive value for sepsis development, though uncertainty around these results exists. The aim of this meta-analysis was to assess the prognostic ability of SDC-1 in predicting sepsis-related complications and mortality. Methods: We searched PubMed, EMBASE, Cochrane Library, and Google Scholar databases from January 01, 1990, to March 17, 2021, to identify eligible studies. The search terms used were "SDC-1, " "sepsis, " "severe sepsis, " and "septic shock, " and a meta-analysis was performed using the RevMan 5.4 software. Results: Eleven studies with a total of 2,318 enrolled patients were included. SDC-1 concentrations were significantly higher in the composite poor outcome group [standardized mean difference (SMD) = 0.55; 95% CI: 0.38-0.72; P < 0.001] as well as in deceased patients (SMD = 0.53; 95% CI: 0.40-0.67; P < 0.001), patients with septic shock (SMD = 0.81; 95% CI: 0.36-1.25; P < 0.001), and patients with acute kidney injury (SMD = 0.48; 95% CI: 0.33-0.62; P < 0.001). Statistical significance was also found in the subgroup analysis when stratified by different sepsis diagnostic criteria. Conclusion: Baseline SDC-1 levels may be a useful predictor of sepsis-related complications and mortality.