INTRODUCTION: Sepsis is a global health threat that has a high incidence and mortality rate. Early prediction of sepsis onset can drive effective interventions and improve patients' outcome. METHODS: Data were collected retrospectively from a cohort of 2,329 adult patients with positive bacteria cultures from a tertiary hospital in China between October 1, 2019 and September 30, 2020. Thirty six clinical features were selected as inputs for the models. We trained models in predicting sepsis by machine learning (ML) methods, including logistic regression, decision tree, random forest (RF), multi-layer perceptron, and light gradient boosting. We evaluated the performance of the five ML models and the evaluation metrics were: area under the ROC curve (AUC), accuracy, F1-score, sensitivity and specificity. The data of another cohort of 2,286 patients between October 1, 2020 and April 1, 2022 were used to validate the performance of the model performing best in the in the internal validation set. Shapley additive explanations (SHAP) method was applied to evaluate feature importance and explain the predictions of this model. RESULTS: Of the five machine learning models developed, the RF model demonstrated the best performance in terms of AUC (0.818), F1 value (0.38), and sensitivity (0.746). The RF model also has a comparable AUC (0.771) in the external validation set. The SHAP method identified procalcitonin, albumin, prothrombin time, and sex as the important variables contributing to the prediction of sepsis. DISCUSSION: The RF model we developed showed the greatest potential for early prediction of sepsis in admitted patients, which could aid clinicians in their decision-making process. Our findings also suggested that male patients with bacterial infections and high procalcitonin levels, lower albumin levels, or prolonged prothrombin times were more likely to develop sepsis.