Copeptin is a new biomarker of cardiovascular diseases. Its diagnostic value in degenerative aortic valve stenosis (AS) with preserved left ventricle systolic function is unknown. We aimed to assess the association of serum copeptin levels with AS severity and coexistence of coronary artery disease (CAD). Sixty-four patients with AS and preserved left ventricle systolic function including 40 with severe degenerative AS (group sAS, effective orifice area EOA = 0.67 cm(2)) and 24 with moderate degenerative AS (group mAS, EOA = 1.40 cm(2)) were enrolled into the study. Twenty-three patients without AS and heart failure, matched for age, sex, and CAD occurrence served as the control group (group C). Serum levels of copeptin and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured using enzyme-linked immunosorbent assay. The mean serum copeptin concentrations were significantly higher in patients with AS: sAS (405 pg/ml) and mAS (351 pg/ml; sAS vs mAS P < 0.05), compared with group C (302 pg/ml, P < 0.05). Serum copeptin levels correlated inversely with EOA (r = -0.55; P < 0.001) in AS patients. There was no correlation between copeptin and NT-proBNP or association with the coexisting CAD. Receiver-operating characteristics analysis showed that copeptin was a good marker of severe/moderate AS (sensitivity 71 %; specificity 87 %), with the optimized cut-off value of 354 pg/ml. Serum copeptin concentration constitutes a novel biomarker of degenerative AS. Coexisting CAD does not interfere with copeptin level.