SUMMARY OBJETIVE Coronavirus disease 2019 (COVID-19) has quickly turned into a health problem globally. Early and effective predictors of disease severity are needed to improve the management of the patients affected with COVID-19. Copeptin, a 39-amino acid glycopeptide, is known as a C-terminal unit of the precursor pre-provasopressin (pre-proAVP). Activation of AVP system stimulates copeptin secretion in equimolar amounts with AVP. This study aimed to determine serum copeptin levels in the patients with COVID-19 and to examine the relationship between serum copeptin levels and the severity of the disease. METHODS The study included 90 patients with COVID-19. The patients with COVID-19 were divided into two groups according to disease severity as mild/moderate disease (n=35) and severe disease (n=55). All basic demographic and clinical data of the patients were recorded and blood samples were collected. RESULTS Copeptin levels were significantly higher in the patients with severe COVID-19 compared with the patients with mild/moderate COVID-19 (p<0.001). Copeptin levels were correlated with ferritin and fibrinogen levels positively (r=0.32, p=0.002 and r=0.25, p=0.019, respectively), and correlated with oxygen saturation negatively (r=-0.37, p<0.001). In the multivariate logistic regression analysis, it was revealed that copeptin (OR: 2.647, 95%CI 1.272–5.510; p=0.009) was an independent predictor of severe COVID-19 disease. A cutoff value of 7.84 ng/mL for copeptin predicted severe COVID-19 with a sensitivity of 78% and a specificity of 80% (AUC: 0.869, 95%CI 0.797–0.940; p<0.001). CONCLUSION Copeptin could be used as a favorable prognostic biomarker while determining the disease severity in COVID-19.