The aim of this study was to determine oxidative stress in patients with untreated chronic hepatitis C (CHC), relating the obtained results with iron status and disease activity markers. Two groups (CHC patients and controls) were studied. CHC patients presented significantly higher values than the control group in some parameters: ALT, AST, GGT, iron, ferritin, and transferrin saturation, and also in tert-butyl hydroperoxide initiate chemiluminescence and thiobarbituric acid-reactive substances (TBARS) as well as lower values in total radical-trapping antioxidant parameter (TRAP). TBARS showed a significant correlation with serum AST and with transferrin saturation, whereas TRAP correlated inversely with serum albumin. Serum ferritin correlated with ALT and GGT, whereas serum iron did so with GGT. In conclusion, lower antioxidant capacity, higher levels of pro-oxidants activity, and iron overload occur in untreated patients with CHC. This greater oxidative activity could play an important role in pathogenesis and evolution of hepatitis C and thus further investigations.