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Buffalo mange is a contagious skin disease caused by a variety of parasitic mites burrowing in or living on the skin. A female Murrah buffalo was presented with a history of inappetence, sudden decrease in milk yield, bilateral lameness of forelimbs with local hair loss and pruritis. Skin scrapings examination revealed presence of both Sarcoptes and Psoroptes mites. A part of the skin scrapings inoculated on various culture media and stained by Gram’s staining showed gram positive cocci bacteria in clumps. Further identification of bacteria by various biochemical tests confirmed the presence of Staphylococcus aureus as a secondary invader. Antibiotic sensitivity test was performed using eight different commonly used antibiotics. Haematology revealed reduced haemoglobin, PCV and TEC values, leucocytosis, neutrophilia and eosinophilia. The buffalo was treated with 1% Ivermectin at 200 µg/kg body weight, subcutaneously once a week for three weeks, Enrofloxacin at 5 mg/kg body weight, intramuscularly once a day for five days and Meloxicam at 0.5 mg/Kg body weight, once a day, intramuscularly for 5 days. Deltamethrin was also applied to the surrounding environment twice at a two week interval. The buffalo showed significant improvement after the treatment.