Sepsis is a severe condition with high mortality, in which immune dysfunction plays a critical role. Poor oral health has been linked to frailty, but its impact on sepsis outcomes remains unclear. Therefore, we used a mouse model of malocclusion and sepsis to investigate how tooth loss affects immune responses during sepsis. Adult male C57BL/6 mice were divided into four groups: Control, Malocclusion (Mal), Sepsis (CS), and Malocclusion with Sepsis (Mal + CS). Malocclusion was induced by tooth extraction, and sepsis was induced using cecal slurry injection. We assessed survival rates, immune cell counts, and biochemical markers. The Mal + CS group exhibited significantly lower survival rates and greater weight loss compared to the CS group. The flow cytometry showed reduced neutrophils, monocytes, and T cells in the Mal + CS group. Elevated ALT and AST levels indicated liver damage. No significant differences in bacterial loads were observed, but immune suppression was exacerbated in the Mal + CS group. Malocclusion worsens sepsis outcomes by impairing both innate and adaptive immune responses. These findings emphasize the importance of oral health in improving sepsis prognosis and immune function during critical illnesses.