The present study was designed to evaluate serum biochemical parameters in twenty local bred sheep infected with Foot-and-Mouth disease virus (FMDV) serotype O. Ten healthy sheep were used as controls. Peripheral blood was collected from both diseased and control group and serum was separated which was further used to estimate the concentration of glucose, total protein, albumin, urea, calcium, phosphorus, cholesterol and activity of AST, ALT and ALP. It was found that there was a significant increase in glucose, AST and phosphorus in FMD affected sheep (p<0.01). Total protein, albumin, calcium, cholesterol and urea level were significantly lower (p<0.05) in FMD group compared to those in the control group. The biochemical alteration indicates the development of pancreatic dysfunction in Foot and Mouth disease affected sheep with FMDV serotype O.