In 2020, the lockdown of Wuhan due to the outbreak of COVID-19 impacted various aspects of local college students' life and may further negatively affect their psychological state. This study was conducted among 652 Wuhan local college students during the quarantine of this city. We assessed their psychological state using Depression-Anxiety-Stress Scale 21 and evaluated their living condition including diet, schedule, recreational activities, social contact, academic life, and attention paid to pandemic news. Results showed that 16.87% of the students reported stress, 28.68% with anxiety, and 35.12% had depression. According to multivariate logistic regression analysis, having a medical background was associated with higher stress levels; students who had an irregular diet and schedule were more likely to develop stress, anxiety, and depression; students with their academic life affected had a higher prevalence of anxiety and depression. By studying local students in the hardest-hit area during the pandemic, our findings can provide references for the improvement of college students' mental health in the long term.