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Background. Copeptin has been implicated as an effective prognostic biomarker of stroke outcome; however, few studies have investigated whether copeptin could be used as an etiological factor for stroke or not. The aim of our study was to evaluate the association of serum copeptin with stroke. Methods. In total, 238 participants including 119 cases (87 ischemic stroke and 32 hemorrhagic stroke) and 119 controls were included in this 1 : 1 matched case-control study. Conditional multivariate logistic regression was conducted to assess the Odds Ratios (ORs) and 95% confidence intervals (CI); restricted cubic spline in logistic regression model was used to evaluate the dose-response association between serum copeptin and total stroke, ischemic stroke, and hemorrhagic stroke. Results. The median serum copeptin was 20.90 pmol/L, 20.90 pmol/L, 6.53 pmol/L, and 8.42 pmol/L for total stroke, ischemic stroke, hemorrhagic stroke, and healthy subjects, respectively. The corresponding ORs (95% CIs) for the highest compared with the lowest quartile were 1.23 (0.62–2.44) for total stroke, 4.01 (1.47–10.96) for ischemic stroke, and 0.13 (0.22–0.69) for hemorrhagic stroke. No nonlinear dose-response relationship was found between serum copeptin and total stroke (Pnonlinear=0.278), ischemic stroke (Pnonlinear=0.362), and hemorrhagic stroke (Pnonlinear=0.314). Compared with the reference copeptin level, a significantly increasing trend was found between serum copeptin and ischemic stroke (Poverall=0.002), and a decreasing trend was found between serum copeptin and hemorrhagic stroke (Poverall=0.007). Conclusions. Elevated serum copeptin levels were positively associated with ischemic stroke and adversely associated with hemorrhagic stroke. Additional prospective studies with larger sample size are needed to confirm the present findings. [ABSTRACT FROM AUTHOR]