As the human population continues to grow, the demand for pork increases, and the management of infectious diseases in swine from a One Health standpoint is becoming more important than ever. To prevent antimicrobial use as much as possible, the search continues for alternative substances that can aid in mitigating oxidative stress and inflammation, which are cornerstones of infectious disease. In this study, we stimulated porcine peripheral mononuclear blood cells (pPBMCs) with either bacterial lipopolysaccharides (LPS) of different origin (Salmonella Typhimurium, Salmonella Enteritidis and E. coli), or the plant lectins concanavalin A (ConA) and phytohemagglutinin (PHA) to create an in vitro inflammatory model. Quercetin, a flavonoid with well documented positive effects, was used with the aim of decreasing oxidative stress and the production of the inflammatory cytokines IL-6 and IL-8. Oxidative stress was successfully induced in the pPBMCs by all stimulants (except for S. Enteritidis LPS), along with IL-6 production (except for E. coli LPS); IL-8 production was only induced by treatment with LPS. While quercetin had an antioxidant effect on the pPBMCs, it did not reduce IL-6 or IL-8 levels under the conditions tested and even had a pro-inflammatory effect by increasing IL-8 production when combined with LPS. To gain a deeper understanding of the immunomodulatory effects of quercetin on pPBMCs, further studies should be conducted to measure the production of additional pro- and anti-inflammatory cytokines, including TNF-α, IL-10, and IL-1β.