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Purpose: The purpose of this study was to investigate the effect of coronavirus disease-19 (COVID-19) knowledge, anxiety, and psychosocial well-being on the infection prevention behavior of college students in health care. Methods: This study is a descriptive survey research. A total of 301 college students at four health care departments in three regions were surveyed using a structured questionnaire from February 10 to February 16, 2022. The collected data were analyzed using descriptive statistics, independent t-test, and one-way ANOVA. Pearson correlation coefficients and multiple regression analyses were done using SPSS ver. 18.0. Results: Knowledge on COVID-19 was significantly dependent on a family history of chronic disease(p=.049). Anxiety was significantly dependent on test of COVID-19 (p=.040). Gender (p=.049), perceived physical and mental health status (p=.000), and chronic disease (p=.000) had significant effects on infection prevention behavior. When the level of anxiety was higher, the infection prevention behavior was also higher (p=.000) and the psychosocial well-being was improved (p=.017). Stepwise multiple regression analysis revealed that anxiety significantly improved the infection prevention behavior (β=.396, p<.001) and psychosocial well-being (β=-.139, p=.008), which accounts for 18.5% (F=22.444, p<.001) of the variance. Conclusion: In order to prevent infectious diseases such as COVID-19 and its spread, measures to prevent infection and improve the psychosocial well-being should also be sought.