Purpose: This study investigated the effects of major satisfaction, academic self-efficacy, and clinical practice stress on college student burnout among nursing students. Methods: Data were collected from October 2019 to January 2020. The data were collected from third and fourth-grade nursing students enrolled at different universities in Seoul, Gyeonggi-do, Chungcheong-do, and Gangwon-do. A total of 270 questionnaires were used for data analysis. Multiple regression analysis was performed to analyze the factors affecting college student burnout. Results: The major satisfaction total score was 65.25(±12.64). The academic selfefficacy total score was 86.56(±13.39). The total clinical practice stress score was 72.93(±11.88). The total score for burnout among college students was 53.73(±14.75). The explanatory power of major satisfaction, academic self-efficacy, and clinical practice stress for college student burnout was 51.3%. Conclusion: It is necessary to develop and apply an educational program to improve major satisfaction and academic self-efficacy, and lower clinical practice stress to reduce college student burnout among nursing students. Thus, education should be actively applied using simulations.