The aim of this study was to determine the possible variations in metabolic profile as well as the pathological findings in naturally infected buffaloes with foot and mouth disease (FMD) during the disease outbreak in 2012. A total number of 25 buffaloes, aged 1 – 5 years, were used in this study. Of these, 15 buffaloes showed characteristic clinical signs of FMD in the form of oral lesions and sudden deaths in young animals. The remaining 10 animals were used as controls. Blood samples were used to establish total white blood cells (WBCs), total red blood cells (RBCs), packed cell volume (PCV%) and haemoglobin concentration (Hb). Specimens from tongue, heart, liver, lung and kidneys were taken for histopathological examination. Hematological analysis revealed lymphocytic leukocytosis. Serum biochemical analysis showed significant increase of AST (P<0.01) and globulins (P<0.05). Venous blood gas analysis indicated metabolic acidosis in diseased buffaloes. From histopathological view, the FMD outbreak was characterized by vesicular stomatitis, interstitial myocarditis and pulmonary oedema.