Background: Student mental health in higher education has been an increasing concern. The COVID-19 pandemic situation has brought this vulnerable population into renewed focus. Objective: Our study aims to conduct a timely assessment of the effects of the COVID-19 pandemic on the mental health of college students. Methods: We conducted interview surveys with 195 students at a large public university in the United States to understand the effects of the pandemic on their mental health and well-being. The data were analyzed through quantitative and qualitative methods. Results: Of the 195 students, 138 (71%) indicated increased stress and anxiety due to the COVID-19 outbreak. Multiple stressors were identified that contributed to the increased levels of stress, anxiety, and depressive thoughts among students. These included fear and worry about their own health and of their loved ones (177/195, 91% reported negative impacts of the pandemic), difficulty in concentrating (173/195, 89%), disruptions to sleeping patterns (168/195, 86%), decreased social interactions due to physical distancing (167/195, 86%), and increased concerns on academic performance (159/195, 82%). To cope with stress and anxiety, participants have sought support from others and helped themselves by adopting either negative or positive coping mechanisms. Conclusions: Due to the long-lasting pandemic situation and onerous measures such as lockdown and stay-at-home orders, the COVID-19 pandemic brings negative impacts on higher education. The findings of our study highlight the urgent need to develop interventions and preventive strategies to address the mental health of college students.