ObjectiveCollege students are one of the most vulnerable populations to the COVID-19 pandemic's mental health effects. During the coronavirus disease 2019 (COVID-19) outbreak, we wanted to see how common depressive symptoms were among college students and what factors contributed to that.MethodsBetween 21 and 27 May 2021, 140,259 college students from three cities in Henan Province, China, were involved. The Patient Health Questionnaire-9 was used to determine depressive symptoms (PHQ-9). Multiple logistic regression analysis was used to calculate odds ratios (ORs) and 95% CIs for potential depressive symptom factors.ResultsMild depressive symptoms and above are present in 21.12% of college students. Women had a higher prevalence of mild depressive symptoms than men (61.38 vs. 59.75%), and depressive symptoms were most prevalent among rural students and least prevalent among city students (21.44 vs. 20.29%). Participants with depressive symptoms are also more likely to have a poor-behavioral status. From none-to-severe depressive symptoms, 78.88, 15.78, 2.80, 1.67, and 0.88% had them. Gender, residential location, and behavioral status were found to be associated with depressive symptoms after adjusting for potential confounders.ConclusionThis cross-sectional study identified the factors that influence the prevalence of depression in college students. It found that the government should pay more attention to mental health issues affecting college students in combating the COVID-19 epidemic normalization.