Abstract: Objective To investigate the mental health status of college students during the epidemic of COVID-19 and identify the factors influencing the mental health of the students. Methods Using a general questionnaire, a self-designed new coronavirus pneumonia knowledge and cognitive behavior questionnaire, the Generalized Anxiety Disorder 7 (GAD-7) and Patient Health Questionnaire 9 (PHQ-9), we conducted an internet-based questionnaire survey of 3881 college students in Guangdong Province. A multinomial-logistic regression model was used to analyze the collected data. Results The survey showed that 69.47% of the college students had a high level of awareness of COVID-19; the overall incidence of anxiety was 26.60% , and the incidences of mild, moderate and severe anxiety were 23.19% , 2.71% , and 0.70% , respectively. Depressive emotions were detected in 21.16% of the students, and the incidences of mild, moderate, and moderate-to-severe depression were 16.98%, 3.17%, and 1.01%, respectively. The results of multivariate analysis showed that an older age was associated with a higher level of awareness of COVID-19 and greater changes in future health behaviors were associated with less anxiety and depression among the students. The students currently in rural areas, of non-medical majors, and reporting half of their information concerning the epidemic being negative were more likely to have anxiety; female gender, residence in suburbs, a drinking history, and excessive negative information concerning the epidemic were all associated with the likeliness of depression. Conclusion The college students have different levels of anxiety and depression during the epidemic. Depression and anxiety are closely related, but the factors contributing to different levels of such emotions can be different, and colleges and related departments are urged to provide precision mental health education for college students.