Troponin-I, homocysteine, Creatine kinase-myocardial band, lactate dehydrogenase and acute phase response had been evaluated in calves with myocarditis due to FMD. The study was conducted on 52 local breed calves 1-6 months old and from both sexes, their dams have no history for vaccination against FMD and show classical foot and mouth disease signs. Ten clinically healthy calves of the same ages were considered as controls. Suspected calves neither show oral blisters, rope salivation, nor foot lesions. Diseased calves showed signs of dullness, in activity, panting with mouth breathing, unable to suck, recumbency, However, five of diseased calves were died within 24-72 hours and on macroscopic examinations of autopsied animals, necrotic myocarditis with pale foci with a zone of hyperemia which were present on the papillary and ventricular cardiac muscles, moreover, on histopathological examinations there were severe inflammatory cells infiltration in the interstitial of myocardial fibers with obvious area of coagulation of myocardial fibers and marked area of hyalinization, furthermore, severe mononuclear cells infiltration, mainly lymphocytes, with few neutrophils closed to necrotic myocardial fibers were also detected. Diagnosis of FMD virus was confirmed by using commercially NSP ELISA kits for foot and mouth. A significant increase (p>0.05)was encounteredin body temperature, respiratory and heart rates in diseased animals than in controls, Furthermore, abnormal cardiac sounds (organic murmurs) were indicated on auscultation of the heart. Results of hematological parameters shown a significant increase indicated in ESR values of diseased calves than in controls, moreover, total leukocyte count was increased significantly with significant lymphocytosis. Furthermore, the results were also showed significant increase in values of serum cardiac troponin, homocysteine, creatine kinase-myocardial band, lactate dehydrogenase, haptoglobin and fibrinogen in seropositive calves for FMD compared with controls. It can be concluded that determination of cardiac biomarkers and acute phase response concentration in calves with myocarditis can considered as a guide to quantify early heart damage.