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Vaccination is one of the best methods of disease controlling in livestock. The present study was conducted to evaluate the stress and haematological changes in buffaloes after the Foot-and-mouth disease vaccination. Ten apparently healthy buffaloes were selected for study and vaccinated with inactivated trivalent (virus types O, A, Asia 1) oil adjuvant Foot-and-Mouth disease vaccine. Whole blood and serum were collected on the day of vaccination, 15th day and 30th day of post-vaccination for the study. Post-vaccination analysis of the haematology revealed the elevated levels of total leukocyte count, neutrophil, lymphocyte and eosinophil count. Elevated levels of serum cortisol levels were noticed immediately by the 15th day of post-vaccination and elevated levels of total protein, serum albumin, aspartate aminotransferase, blood urea nitrogen levels were noticed by the 30 days of post vaccination. Study findings support the development of the immunity against the vaccination and stress immediately after the vaccination in buffaloes.