Ovine respiratory complex is a significant cause of death in sheep flocks, where Pasteurella multocida is the most frequent microorganisms isolated from animals with pneumonia. There is an urgent need to refine the use of different antimicrobials to avoid the problem of antimicrobial resistance and optimize the control of this disease in ovine livestock. The first step in approaching this problem is gaining an insight into the antimicrobial susceptibility of ovine pathogens. This study evaluated the in vitro activity of tildipirosin, gamithromycin, oxytetracycline, and danofloxacin against Pasteurella multocida strains isolated from sheep with fibrinous pneumonia. The strains were incubated following Clinical and Laboratory Standards Institute (CLSI) standard conditions and also with a modified method by 25% supplementation with sheep serum. Minimum inhibitory concentrations (MIC) were determined using the broth microdilution technique. The lowest MIC90 under standard conditions and by supplementation with sheep serum was obtained with tildipirosin. Sheep serum significantly reduced tildipirosin, gamithromycin, and danofloxacin MIC values for Pasteurella multocida strains. In brief, the potency of tildipirosine, gamithromycin, and danofloxacin against Pasteurella multocida increases when sheep serum is added to the culture media.