<![CDATA[Objectives: To evaluate the prognostic value of interleukin-6 (IL-6) for mortality in intensive care unit (ICU) patients with sepsis.Study design: This study was conducted as a systematic review and meta-analysis of observational studies. Study quality was assessed using the Quality in Prognosis Studies (QUIPS) tool, and adjusted hazard ratios (HRs) were pooled using a random-effects model.Data sources: A comprehensive literature search was performed in PubMed, Scopus, Cochrane Library, and ScienceDirect for studies published up to March 2026. Reference lists of relevant articles were also screened to identify additional eligible studies.Data synthesis: Eighteen studies were included in the qualitative synthesis, and six studies were included in the meta-analysis. Elevated IL-6 levels were consistently higher in non-survivors across studies. The pooled analysis demonstrated that increased IL-6 levels were significantly associated with higher mortality risk (HR = 1.39, 95% CI 1.14–1.70; p = 0.001), with moderate heterogeneity (I² = 70%), likely reflecting differences in study populations, measurement timing, and study design. Sensitivity analysis excluding one large multicenter study reduced heterogeneity (I² = 0%) while maintaining statistical significance (HR = 1.29, 95% CI 1.13–1.47; p < 0.001), confirming the robustness of the findings.Conclusions: Elevated IL-6 is significantly associated with increased mortality in ICU patients with sepsis. Despite heterogeneity, the findings are consistent and support the role of IL-6 as a prognostic biomarker, particularly when integrated with other clinical and laboratory parameters.Registration: The protocol for this systematic review was prospectively registered in PROSPERO.]]>
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