The use of analgesia in bacterial challenge models has been met with some controversy in the literature. Several publications suggest that the use of analgesics in infection models can interfere with the host immune response, change microenvironments subsequently altering bacterial pathogenesis, and directly act as an antimicrobial as was reported with opioids such as morphine. Any such interactions would compromise the experimental results, deterring researchers from the use of analgesia. Herein, we address the possible effect of analgesics on bacterial colonization in a Staphylococcus aureus surgical site infection model in Göttingen minipigs. Retrospectively, an expanded analgesia protocol (buprenorphine presurgery and carprofen postsurgery) was compared with a standard analgesia protocol using buprenorphine alone just before surgery. When examined statistically, the expanded analgesia protocol group was noninferior to the standard analgesia protocol group indicating there was no substantial decrease in bacterial burden when an expanded analgesia protocol was administered. Our results highlight the importance of studying the use of analgesia in all animal models of infection to determine if the analgesics will affect experimental outcomes.