Fasciola hepatica infection results in increased production of reactive oxygen species (ROS) and changes the activity/level of antioxidants in the host organism, which leads to oxidative stress formation and oxidative modifications of lipids and proteins. Taking this into account, the aim of this study was to assess the antioxidant potential and the activity of proteases and their inhibitors in the serum of rats infected with F. hepatica. Wistar rats were infected per os with 30 metacercariae of F. hepatica. The total antioxidant status (TAS) and the activity of cathepsin G and elastase and their inhibitors (alpha1-antitrypsin and alpha2-macroglobulin) were determined at 4, 7, and 10 weeks post infection (wpi). It was confirmed that F. hepatica infection leads to a decrease in the antioxidant capacity of serum, which was manifested as a reduction in total antioxidant status by about 24, 39, and 27%, respectively, at 4, 7, and 10 wpi. At the same time, the activity of proteases increased significantly: cathepsin G by about 25, 37, and 30%, and elastase by about 18, 16, and 9% during the course of F. hepatica infection, compared with the control group. However, the activity of alpha1-antitrypsin was significantly reduced, by 36, 55, and 25%, while alpha2-macroglobulin activity was reduced by about 14, 17, and 8% during the same period of fasciolosis. These results indicate that the shift in protease/antiprotease balance towards protease action observed during the course of fasciolosis may result in a decrease in host antioxidant capacity.