Background: The coronavirus disease 2019 (COVID-19) pandemic continues to affect the mental health of college students in the post-epidemic era. We assessed the status and related factors of college students who are vulnerable to anxiety and depression during the COVID-19 lockdown.

Methods: This cross-sectional study was conducted two weeks after the beginning of the COVID-19 lockdown, from November 6, 2022, to December 2, 2022, with 1176 valid samples using convenience sampling. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to measure levels of anxiety and depression in college students. Factors related to anxiety, depression, and their comorbidity were analyzed using binary logistic regression.

Results: The prevalence of anxiety, depression, and their comorbidity were 27.04%, 34.10%, and 25.60%, respectively. There was a higher risk of anxiety, depression, and their comorbidity among those who were currently living in rural areas. Compared with individuals with low monthly living expenses, those with higher monthly living expenses were less prone to anxiety, depression, and their comorbidity.

Conclusions: High prevalence of anxiety, depression, and their comorbidity were detected among college students during the COVID-19 lockdown. These were most common among college students who were senior students, had abnormal body mass index (BMI), were rural area residents, did study arts and humanities, were one-child in the family, and had low monthly living expenses and poor academic performance. Intervention practitioners and policymakers should formulate individualized prevention and intervention measures during the COVID-19 lockdown in the post-epidemic and possible future pandemics for college students.