A meta-analysis evaluated the effectiveness of blood copeptin levels in predicting mortality in adult patients with sepsis. It included ten prospective studies with 1,637 patients where copeptin levels were measured on admission or within 48 hours. Pooled sensitivity was 0.77 (95% CI: 0.70–0.83; I² = 52%) and specificity was 0.76 (95% CI: 0.67–0.83; I² = 86%). Pooled positive odds ratios were 3.16 (95% CI: 2.33–4.29), negative 0.30 (95% CI: 0.23–0.40) and diagnostic odds ratio (DOR) 10.40 (95% CI: 6.62–16.33). The area under the summary curve (AUC) reached 0.83 (95% CI: 0.79–0.86), indicating good prognostic accuracy. Subgroup analysis according to copeptin cut-off values did not significantly influence the results and no publication bias was detected (p = 0.58). Elevated copeptin levels within 48 hours of diagnosis show good accuracy for predicting short-term mortality.