Objective: The objective of this study was to investigate the effect of meloxicam on the pharmacokinetics of cefquinome in experimental endotoxemic sheep. In addition, the MIC of cefquinome was determined against Escherichia coli, Pasteurella multocida, Klebsiella pneumoniae, and Mannheimia haemolytica. Methods: The study was carried out on six sheep in three periods according to a longitudinal pharmacokinetic design. Cefquinome (2.5 mg/kg, IV, CFQ) was administered in the first period, cefquinome+meloxicam (1 mg/kg, IV, CFQ+MLX) in the second period, and lipopolysaccharide (20 µg/kg, IV, LPS+CFQ+MLX)+meloxicam+cefquinome in the third period. Plasma cefquinome concentrations were assayed using HPLC-UV, and pharmacokinetic data were calculated by a two-compartment open model. Results: Following a single IV injection of cefquinome, the t1/2β, Vdss, and ClT values were 1.12 h, 0.21 L/kg, and 0.17 L/h/kg, respectively. The t1/2β was prolonged from 1.12 to 2.79 h in the LPS+CFQ+MLX group. While Vdss was increased (from 0.21 to 0.36 L/kg) in the LPS+CFQ+MLX group, ClT decreased (from 0.17 to 0.10 L/h/kg) in the CFQ+MLX and LPS+CFQ+MLX groups. The MICs of cefquinome were 0.031 to 0.063 µg/mL for E. coli, M. haemolytica, and K. pneumoniae and 0.016 to 1 µg/mL for P. multocida. At a 12 h dosing interval, the CFQ, CFQ+MLX, and LPS+CFQ+MLX groups attained a T > MIC ratio of 40% for bacteria with MIC values of ≤ 0.50, ≤ 1, and ≤ 1 µg/mL, respectively. Conclusion: These results indicate that combined administration of meloxicam alters the pharmacokinetics and therapeutic efficacy of cefquinome in experimental endotoxemic sheep.