Background: The study aimed to investigate the association between comorbid Type 2 diabetes mellitus (T2DM) and sepsis outcomes with new evidence and compare the immunity responses of sepsis patients with T2DM and nondiabetics. Methods: We conducted a retrospective data collection from consecutive patients diagnosed with sepsis. Utilizing propensity score matching (PSM), we matched T2DM patients with non-diabetics. We subsequently performed a comparative analysis of immune markers and primary clinical outcomes. Results: 801 sepsis patients (322 with T2DM and 475 non-T2DM) were included. Following the PSM, sepsis patients with comorbid T2DM exhibited a reduced risk of 28-day (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.41-0.94; P=0.031) and 90-day (OR: 0.64; 95% CI: 0.45-0.89; P=0.010) in-hospital mortality. There were no statistically significant differences in acute lung injury (OR: 0.80, 95% CI: 0.52-1.22, P=0.328), acute kidney injury (OR: 0.86, 95% CI: 0.56- 1.32, P=0.510), the length of hospital stays between the groups (Table 2). Notably, T2DM patients showed elevated levels of lymphocytes and C4, while their IGM and IGG levels were lower than non-diabetics. Conclusion: T2DM is associated with a reduced risk of 28-day, 90-day in-hospital mortality in sepsis. The risk of acute lung injury, or acute kidney injury and length of hospital stay was similar among T2DM and non-diabetics. Sepsis patients with comorbid T2DM exhibit enhanced levels of lymphocytes and C4 but reduced levels of IGG and IGM compared to non-diabetics.