Objective <p>Sepsis is a syndrome of systemic inflammatory reaction caused by a severe infection, leading to multiorgan damage and a high mortality rate. In recent years, several studies have shown that decoy receptor 3 (DcR3) is positively correlated with the severity of infection, and its high specificity and sensitivity in the diagnosis of sepsis is expected to serve as a novel marker for sepsis. This meta-analysis aims to evaluate the diagnostic accuracy of decoy receptor 3 (DcR3) for sepsis in the intensive care unit (ICU) setting.</p> Methods <p>We conducted a comprehensive search in six databases, extracting data independently.Studies were included if they assessed the diagnostic accuracy of DcR3 for sepsis in the intensive care unit (ICU). A meta-analysis was performed using a random-effects model to calculate pooled sensitivity, specificity, and area under the curve (AUC).</p> Results <p>Four records assessing 681 patients were included in this meta-analysis. In distinguishing sepsis from normal controls, DcR3 demonstrated exceptional discriminatory power with an AUC of 0.99. The pooled sensitivity was 0.98 (95% CI 0.95–0.99), and the pooled specificity was 0.95 (95% CI 0.92–0.97). The pooled PLR was 21.21 (95% CI 12.71–35.40), the pooled NLR was 0.02 (95% CI 0.01–0.06), and the pooled DOR was 878.26 (95% CI 217.36–21062.55). In differentiating sepsis from systemic inflammatory response syndrome (SIRS), the AUC was 0.95. The pooled sensitivity was 0.93 (95% CI 0.87–0.96), and the pooled specificity was 0.87 (95% CI 0.68–0.95). The pooled PLR was 6.89 (95% CI 2.67–18.26), the pooled NLR was 0.08 (95% CI 0.04–0.15), and the pooled DOR was 86.17 (95% CI 27.35–271.55).</p> Conclusion <p>On the basis of our meta-analysis, DcR3 is a helpful marker for early diagnosis of sepsis on ICU admission. However, the findings are limited by the small number of included studies and significant heterogeneity. Further large-scale, multicenter prospective studies are warranted to validate these results.</p>