Abstract Objective The aim of this study was to construct interpretable machine learning models to predict the risk of developing delirium in patients with sepsis and to explore the impact of delirium on the 28-day survival rate of patients. Methods We enrolled 10,321 patients with sepsis older than eighteen years from the MIMIC-IV (Medical Information Mart for Intensive Care) database. Sepsis is defined as the presence or suspected presence of infection, along with a SOFA (Sequential Organ Failure Assessment) score of ≥ 2. Four machine learning models, namely XGBoost (extreme gradient Boost), SVM (support vector machine), Logistic (logistic regression) and RF (random forest), were established for prediction, and the prediction model was constructed. Results A total of 10,321 sepsis patients were included, among whom 4,691 (45.45%) developed delirium. The 28-day mortality rate was markedly elevated in the delirium group (log-rank P