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The pharmacokinetics of ceftriaxone, sulbactam individually and in combination (ceftriaxone: sulbactam, 1:1) at 20 mg kg-1 body weight (bw) as single dose intravenous administration (i.v.) was conducted in healthy and experimental Escherichia coli O157:H7 induced mastitis in black Bengal goats. Semi logarithmic plot of plasma ceftriaxone and sulbactam concentrations against time in healthy and mastitis induced goats alone and in combination witnessed 2-compartment models. Ceftriaxone could not be detected in plasma beyond 6 h in individual therapy and 8 h in combination therapy with sulbactam. Ceftriaxone persisted in the milk for longer time in experimental mastitis when given in combination with sulbactam. The lower Cmax milk: Cmax plasma (≤1) values indicated inadequate distribution and penetration of ceftriaxone into the mammary glands in experimental mastitis. Ceftriaxone was rapidly metabolized to ceftizoxime post-dosing which was also detected in the plasma and milk for considerable period of time. Mastitis-challenged goats treated with sulbactam had grave prognosis. Pharmacokinetics of both ceftriaxone and sulbactam got altered in goats post experimental mastitis. The dosage of the drugs in combination therapy of ceftriaxone with sulbactam may be reduced in experimental mastitis compared to healthy goats.