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Purpose: The purpose of the study was to investigate the effect of college life stress and self-efficacy on the well-being of nursing students in the COVID-19 environment. Methods: The subjects of the study were 247 senior nursing students at K University in W City. Data collection was conducted during the period of in-school practice from July 27 to August 10, 2020, using a structured questionnaire. For data analysis, SPSS/WIN 23.0 was used to conduct the t-test, ANOVA, correlation and multiple regression. Results: Factors affecting the subjects’ well-being were grades (t=3.07 p=.002) and major satisfaction (t=2.16 p=.032) among general characteristics. College life stress (t=-5.05, p<.001) was found to have a negative effect on students' well-being, and self-efficacy (t=6.91, p<.001) was found to have a positive effect (F=46.97, p<.001). Conclusion: As a result of the study, college life stress was found to have a negative effect as a factor affecting the subjects’ well-being, while self-efficacy was found to have a positive effect. In conclusion, in order to improve the well-being of nursing students, it is necessary to try various methods to improve self-efficacy and relieve college life stress.