INTRODUCTION: Sepsis associated thrombocytopenia (SAT) is a common complication of sepsis. We designed this study to investigate factors influencing SAT. METHODS: Patients with sepsis (2984 in Peking union medical college hospital [PUMCH] database, 13165 in eICU Collaborative Research [eICU] database, 11101 in Medical Information Mart for Intensive Care IV [MIMIC-IV] database) were enrolled. Variables included basic information, comorbidities, and organ functions. Multi-variable logistic regression models and artificial neural network model were applied to determine the factors related to SAT. MAIN RESULTS: Age and body mass index (BMI) were inversely correlated with the incidence of SAT (p-value 0.175 and 0.049 [PUMCH], p-value 0.000 and 0.000 [eICU], p-value 0.000 and 0.000 [MIMIC-IV]). Hematologic malignancies and other malignancies were positively correlated with the incidence of SAT (p-value 0.000 and 0.000 [PUMCH], p-value 0.000 and 0.000 [eICU], p-value 0.000 and 0.020 [MIMIC-IV]) except other malignancies was inversely correlated with the incidence of SAT in PUMCH database. Norepinephrine (NE) equivalents, total bilirubin (TBIL) and creatinine were positively correlated with the incidence of SAT (p-value 0.000, 0.000 and 0.011 [PUMCH], p-value 0.028, 0.000 and 0.013 [eICU], p-value 0.028, 0.000 and 0.027 [MIMIC-IV]). PaO2 / FiO2 was inversely correlated with the incidence of SAT in PUMCH database (p-value 0.021 [PUMCH]), while it was positively correlated with the incidence of SAT (p-value 0.000 [MIMIC-IV]). PaO2 / FiO2 and SAT was not related (p-value 0.111 [eICU]). TBIL, hematologic malignancies, PaO2 / FiO2 and NE equivalents ranked in the top five significant variables in all three datasets. CONCLUSIONS: Hematologic malignancies and other malignancies were positively correlated with the incidence of SAT. NE equivalents, TBIL and creatinine were positively correlated with the incidence of SAT. TBIL, hematologic malignancies, PaO2 / FiO2 and NE equivalents ranked in the top significant variables in factors influencing SAT.