Purposes: Sepsis is a critical condition in which nurses should detect clinical manifestations and provide early intervention to prevent unwanted serious conditions in the patients. The initial occurrence and management of sepsis take place in general units, but there is a lack of knowledge in nurses. The purpose of this study was to examine the effects of a case-based sepsis education program and compare the case-based education program with and without smartphone applications. Methods: A quasi-experimental pre-test-post-test design with a control group was used. We provided a case-based education program with and without smartphone applications to the nurses and tested the effects of the program on knowledge, the accuracy of sepsis assessment, and self-efficacy as outcome variables. A total of 60 nurses in general units participated. To test differences in knowledge, the accuracy of sepsis assessment, and self-efficacy regarding sepsis between the groups over time, a mixed-design ANCOVA was used for parametric analysis, and generalized estimating equations (GEE) were used for nonparametric analysis. Results: There were significant differences in knowledge, the accuracy of sepsis assessment, and self-efficacy between the groups and within the groups over time. The intervention groups treated with the case-based education program showed improved outcome variables compared to the control group. There was no difference between case-based education with the smartphone application or without the application. Conclusions: The case-based education improved knowledge, the accuracy of sepsis assessment, and self-efficacy in the care of sepsis by nurses working in the general wards. The results suggest that the case-based education program for nurses was effective and eventually improved patient health outcomes.