Chronic hepatitis C virus (HCV) infection plays a pivotal role in hepatocarcinogenesis and has been associated with oxidative DNA damage. Few data have been reported on the general redox state in patients infected with different HCV genotypes. Total antioxidant capacity (TAC) and hydrogen peroxide levels as well as oxidative stress index were measured in serum of hepatitis C chronic patients in relation to genotype, viral load, transaminases level and degree of fibrosis. Serum was obtained from two-hundred-fifty-two HCV infected patients and twenty-five healthy donors. TAC was measured by TAC Colorimetric Assay and hydrogen peroxide concentration by Hydrogen Peroxide Colorimetric Assay Kit. In HCV infected patients, mean serum TAC was 5.62 mM Trolox equivalents which was significantly lower (p < 0.0001) than control group (7.25 mM Trolox equivalents). TAC reduction was particularly evident in patients infected by genotype 2 compared to those infected by genotypes 1, 3 and 4. In parallel, high levels of hydrogen peroxide were found in the serum of infected patients, p=0.0015. Although no statistically significant correlation was found with the degree of fibrosis, transaminases level or viral load, oxidative stress index was higher in HCV infected patients compared to uninfected controls, p=0.003. The results indicate an imbalance of the redox state in HCV infected patients, with a strong reduction of the total antioxidant capacity and high oxidative stress index. Because oxidative burden may favour disease progression, a novel strategy aimed at counteracting it by using antioxidant molecules as adjunct therapy might represent a useful tool in the management of HCV chronic infection.