Background:Sepsis is a syndrome of organ dysfunction caused by the host’s dysregulated response to infection and has a high mortality rate. Preliminary studies have shown that blood type O is significantly associated with poor prognosis of sepsis, but the specific mechanism is not fully understood. The purpose of this study was to explore the correlation between blood group and sepsis prognosis through systematic data analysis, and to provide reference for clinical practice. Methods: A total of 24 patients with sepsis and septic shock treated in the Shenzhen Longhua District People’s Hospital from January 2023 to June 2024 were selected as the research subjects. According to whether the blood type is O divided into the study group and the control group. General clinical data, hematological indexes and prognosis were compared between the two groups. Results: The positive results of bacterial culture were statistically higher in the study group than in the control group; the study group had statistically higher respiratory support than the control group upon admission; the study group had a statistically higher bleeding rate during hospitalization than the control group; and the 30-day mortality rate in the study group was significantly higher than in the control group. Total bilirubin, conjugated bilirubin, and fibrinogen were statistically significantly higher in the study group compared to the control group PCT and IL-6 were statistically significantly higher in the research group compared to the control group; platelet count was statistically significantly lower in the research group compared to the control group. Conclusion: Patients with blood type O are at higher risk of bleeding, making it difficult to treat and at increased risk of death. Therefore, the monitoring and management of bleeding risk in patients with sepsis with blood type O should be strengthened in clinical treatment to reduce mortality.