OBJECTIVES: This study aimed to investigate the relationship between ABO blood group and sepsis-associated thrombocytopenia (SAT). DESIGN AND SETTING: The primary outcome was SAT within the first 72 hours of ICU admission. PATIENTS: The retrospective study included 9113 patients diagnosed with sepsis from January 2014 to December 2022. A total of 6296 patients eventually were included into the study, who were divided into four groups based on ABO blood group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 2494 patients (39.6%) were diagnosed with SAT, and 712 (11.3%) of them experiencing severe SAT. The occurrence of SAT among the ABO blood groups was significantly lower in AB blood group compared with the other groups ( p = 0.032). Individuals in AB blood group were less likely to experience severe SAT ( p = 0.028). In multivariate analysis, B blood group (odds ratio [OR], 1.32
95% CI, 1.05-1.67) and O (OR, 1.37
95% CI, 1.09-1.72) were significantly associated with a higher occurrence of SAT compared with AB blood group. In multivariate analyses, A blood group (OR, 1.68
95% CI, 1.16-2.42), B blood group (OR, 1.74
95% CI, 1.74-2.50), and O blood group (OR, 1.72
95% CI, 1.20-2.48) remained significantly risk factors associated with a higher occurrence of severe SAT compared with AB blood group. CONCLUSIONS: B blood group and O were associated with an increased risk of SAT and severe SAT.