Pharmacokinetic study was performed in healthy and febrile Ongole calves following single intramuscular administration of pefloxacin @ 10mg/kg body weight. Febrile condition was induced by injecting Escherichia coli endotoxin @ 1 μg/kg body weight intravenously. The concentration time data of pefloxacin in serum was described by one compartment open model with absorption. The drug was detectable for longer time in healthy calves. Ongole calves exhibited higher bio-availability indicating the complete and rapid absorption of pefloxacin. The peak concentration of the drug in serum of healthy calves was significantly higher than in febrile calves while the time to achieve peak concentration was similar in both groups. The other kinetic parameters like absorption half-life, elimination half-life, MRT, AUC and the duration of therapeutic effect were significantly higher in healthy calves, while absorption half-life was higher in febrile calves. Evaluation of pharmacokinetic variables of pefloxacin in healthy and febrile ongole calves after intramuscular administration elucidated that the drug was metabolised and eliminated at faster rate in febrile calves. Febrile calves exhibited lower values for key kinetic parameters like Cmax, Elimination half-life, AUC and duration of therapeutic effect indicating the requirement of more frequent administration during fever.