The COVID-19 pandemic has had a significant effect on the mental health of university students worldwide. The purpose of this study was to investigate changes in depression over a one-year period, during the COVID-19 pandemic (from 2021 to 2022), in a sample of Egyptian college students. University students were invited to complete the Beck Depression Inventory (BDI) twice. Additionally, students were asked to respond to questions on the COVID-19 condition. A total of 722 students completed the BDI twice. At baseline, the prevalence of depression was estimated to be 29.6%, however, the 12-month follow-up examination revealed that 37.8% of students had depression. At two time points, students who had suspected COVID-19 symptoms had significantly higher BDI scores than those who did not. Furthermore, the 12-month examination revealed a significant rise in depression as compared to the baseline assessment. There is an urgent need for specific interventions to address university students' mental health concerns. Priorities should be set for teaching students effective coping mechanisms during times of crisis. The current study highlights the impact of the COVID-19 pandemic on mental health.