BACKGROUND: Serum cardiac troponin (cTn) elevation is a well-established phenomenon in sepsis. However, the clinical significance of this phenomenon with high-sensitivity (hs) assays and the current sepsis definition needs to be settled. RESEARCH QUESTION: What is the association between early serum cTn levels measured by hs-assays and the risk of short-term mortality in septic patients? STUDY DESIGN AND METHODS: We conducted a systematic review using a comprehensive PubMed, Scopus, and Embase search. Studies were eligible if they reported association data on early hs-cTn and mortality in an adult sample with sepsis that met the Sepsis-3 definition. For the synthesis of the effect of hs-cTn on mortality, we applied random effect models on the pooled unadjusted and adjusted odds ratio (OR and aOR, respectively) of elevated vs. normal hs-cTn serum values, and on the crude standardized mean difference (SMD) of hs-cTn between survivors and non-survivors. RESULTS: In total, 6242 patients from 17 studies were included, with short-term mortality rates ranging from 16.9% to 53.8%. Using a crude analysis, non-survivor patients showed higher hs-cTn than survivors (SMD of 0.87, 95%CI: 0.41-1.33). Elevated hs-cTn was associated with increased mortality (OR = 1.78, 95% CI: 1.41-2.25). However, this prognostic effect was absent in studies that adjusted for different confounders (aOR = 1.06, 95% CI: 0.99-1.14). DISCUSSION AND CONCLUSIONS: Non-survivors of sepsis exhibited significantly elevated hs-cTn levels. While elevated hs-cTn levels are associated with an increased risk of mortality, they are not independently associated with this outcome in sepsis.