Sepsis is an inflammation caused by the body's systemic response to an infection. The infection could be a result of many diseases, such as pneumonia, urinary tract infection, and other illnesses. Some of its symptoms are fever, tachycardia, tachypnea, etc. Unfortunately, sepsis remains a critical problem at the hospitals and leads to many issues, such as increasing mortality rate, health care costs, and health care utilization. Early detection of sepsis in patients can help respond quickly, take preventive actions, and prevent major issues. The main aim of this study is to predict the risk of sepsis by utilizing the patient’s demographic and clinical information, i.e., patient’s gender, age, severity level, mortality risk, admit type along with hospital length of stay. Six machine learning approaches, Logistic Regression (LR), Naïve Bayes, Support Vector Machine (SVM), Boosted Tree, Classification and Regression Tree (CART), and Bootstrap Forest are used to predict the risk of sepsis. The results showed that different machine learning methods have other performances in terms of various measures. For instance, the Bootstrap Forest machine learning method exhibited the highest performance in AUC and R-square or SVM and Boosted Tree showed the highest performance in terms of misclassification rate. The Bootstrap Forest can be considered the best machine learning method in predicting sepsis regarding applied features in this research, mainly because it showed superior performance and efficiency in two performance measures: AUC and R-square.