Background: Pasteurella multocida is the etiological agent responsible for several diseases in a wide range of hosts around the world and thus, causes serious economic losses. Acute septicemia associated with capsular type B P. multocida has recently emerged in Europe and continuous outbreaks of these acute processes have been described in Spain since they were first detected in pigs in 2009 and cattle in 2015. The scarcity of studies on the antimicrobial susceptibility of this capsular type of P. multocida and growing concern about the general increase of antimicrobial resistance mean that studies related to the performance of type B P. multocida against antibiotics are necessary to establish accurate treatments and to monitor antimicrobial resistances. Results: Seventy-six isolates of P. multocida type B from pigs and cattle with acute septicemia were tested for susceptibility to 10 different antimicrobials. Bovine isolates were susceptible to all the antibiotics we tested except for lincomycin (94.4% of isolates were resistant). However, the antimicrobials we tested were less effective against swine isolates, of which none were susceptible to lincomycin. Furthermore, 29.3% swine isolates were resistant to tetracycline, 27.6% to penicillin, 20.7% to oxytetracycline, 17.3% to chloramphenicol, 15.5% to gentamicin, and 3.4% to enrofloxacin; no resistance to ceftiofur was detected. No multidrug resistant isolates were detected from cattle, while 25.86% of swine isolates were resistant to three or more antibiotic classes. Conclusions: In this study, the lower resistance rates and multidrug resistant isolates reported for P. multocida type B derived from cattle compared to those isolated from pigs may be related to the increased use of antibiotics in the porcine industry in Spain. Lincomycin is not recommended for the treatment of acute septicemia in pigs or cattle, rather, the use of ceftiofur, enrofloxacin, or gentamicin is indicated as an emergency treatment in the early stages of disease; once the susceptibility results are known, the use of tetracyclines, penicillin, or chloramphenicol should be prioritized. The increase in multidrug resistant isolates and antimicrobial resistance rates indicates that more attention should be paid to prevention as well as the responsible use of antibiotics.