Foot-and-mouth disease (FMD) is an acute, contagious viral disease in cattle that is associated with enormous economic losses in Turkey and worldwide. The purpose of this study was to determine changes in serum malondialdehyde (MDA), coenzyme Q10 (CoQ10), 8-hydroxydeoxyguanosine (8-OHdG) and deoxyguanosine (dG) and to perform histopathological examinations in calves with FMD. Thirty calves were studied, 20 of which were infected with FMD and 10 were free of the disease. Following a routine clinical examination, blood samples were obtained, and serum MDA, CoQ10, 8-OHdG and dG levels were determined. Necropsy and histopathological examinations were performed on dead calves with FMD. MDA and 8-OHdG/106dG levels were significantly higher in calves with FMD than in the control group. However, the increase in CoQ10 levels in calves with FMD, compared with the control group, was not statistically significant. Macroscopic examination of the heart tissue of calves with acute myocarditis revealed the presence of pale, yellowish gray-white necrotic muscle fibers in the ventricular wall of the heart. The muscle fibers in the myocardium were swollen and exhibited pyknotic nuclei and intense lymphocytic cell infiltration. In longitudinal sections, the muscle fibers were non-striated, swollen, and homogenously pink and contained pink nuclei. Between muscle fibers, intense mononuclear cell infiltration was observed. The findings of the present study indicate that oxidative stress is significantly increased in calves with FMD, and that oxidative DNA damage may play an important role in the etiopathogenesis of FMD. This is the first study to report CoQ10 and 8-OHdG levels in calves with FMD, and its findings may serve as the basis for future studies on this subject.