Objectives To explore the utility of radiomics and deep learning model in assessing the risk factors for sepsis after flexible ureteroscopy lithotripsy (FURL) or percutaneous nephrolithotomy (PCNL) in patients with ureteral calculi. Methods This retrospective analysis included 847 patients with treatment-naive proximal ureteral calculi who received FURL or PCNL. All participants were preoperatively conducted non-contrast computed tomography scans, and relevant clinical information was meanwhile collected. After propensity score matching, the radiomics model was established to predict the onset of sepsis. A deep learning model was also adapted to further improve the prediction accuracy. Performance of these trained models was verified in another independent external validation set including 40 cases of ureteral calculi patients. Results The overall incidence of sepsis after FURL or PCNL was 5.9%. The least absolute shrinkage and selection operator (LASSO) regression analysis revealed 26 predictive variables, with an overall AUC of 0.881 (95% CI, 0.813-0.931) and an AUC of 0.783 (95% CI, 0.766-0.801) in external validation cohort. Judicious adaption of a deep neural network (DNN) model to our dataset improved the AUC to 0.920 (95% CI, 0.906-0.933) in the internal validation. To eliminate the overfitting, external validation was carried out for DNN model (AUC = 0.874 (95% CI, 0.858-0.891)). Conclusions The DNN was more effective than the LASSO model in revealing risk factors for sepsis after FURL or PCNL in single ureteral calculi patients, and females are more susceptible to sepsis than males. Deep learning models have the potential to act as gatekeepers to facilitate patient stratification.