Glucagon like peptide 1 receptor (GLP 1R) agonists such as semaglutide is considered as promising agents due to their ability to promote sustained weight loss. Obesity is associated with an increased risk of septic arthritis due to impaired immune responses and low grade chronic inflammation. Septic arthritis commonly caused by Staphylococcus aureus,is an infectious joint disease characterized by synovial inflammation, cartilage destruction and systemic complication that may progress to sepsis and organ dysfunction. The present study aimed at understanding the effect of Semaglutide on disease severity in experimental Staphylococcal Septic Arthritis induced inflammation by Staphylococcus aureus AH5016 in NMRI mice.Female NMRI mice were pre treated with Ozempic/PBS for 14 days subcutaneously prior to infection with S.aureus AH5016 strains intravenously. The clinical course of septic arthritis, body weight, mortality was recorded for 7 days.Bacterial dissemination was studied using IVIS bioluminescence imaging, kidney abscess formation, bacterial burden, and inflammatory cytokine production. There was no significant difference observed in survival, weight loss, clinical arthritis scores and severity with semaglutide treated mice and controls.In vivo and ex vivo IVIS imaging also did not reveal any significant difference in bioluminescence signals in whole body, joints and bacterial burden in kidneys. Plasma concentrations of inflammatory cytokine IL6 and chemokine KC/CXCL1 were also identified, although no significant difference observed. These findings collectively demonstrate that Semaglutidepre treatment did not significantly contribute to clinical course of septic arthritis induced by Staphylococcus aureus infection AH5016 in NMRI mice.