To our knowledge, no study has evaluated N-terminal pro-brain natriuretic peptide (NTproBNP) together with interleukin-6 (IL-6) and interferon (IFN)-gamma serum levels in a large series of patients with hepatitis C virus (HCV) as possible markers of cardiac dysfunction. NTproBNP and IL-6 serum levels were valued in 55 HCV-patients, and in 55 sex- and age-matched controls. HCV-patients showed significantly higher mean NTproBNP and IL-6 levels than controls ( P = 0.001); no significant difference was observed for IFN-gamma. By defining high NTproBNP level as a value higher than 300 pg/mL (that is used to rule out heart failure in patients under 75 years of age), 12% (6/49) of HCV-patients and 0 of controls had NTproBNP (χ²; P = 0.012). In conclusion, this study demonstrates high levels of circulating NTproBNP and IL-6 in HCV-patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction. Further prospective studies quantifying symptoms and correlating these with echocardiography parameters are needed to confirm this association.