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The COVID-19 pandemic has had a great impact on the mental health and well-being of different populations including young adults. This study replicates and extends previous research by evaluating the impact of the COVID-19 pandemic on the well-being of college students in Cyprus, a Mediterranean island with unique sociocultural and genetic characteristics, and to identify risk factors related to the poor mental health of university students. Behavioral changes in the students before and during the quarantine period were also examined. A total of 387 university students completed an online survey coordinated by the Young Universities of Europe (YUFE) network. Results indicated that most of the sample (89.3%) reported depressive symptoms. Academic stress and academic satisfaction were associated with depressive symptoms and loneliness. Specifically, students with greater academic stress and lower academic satisfaction reported more symptoms of depression and felt lonelier. Younger students with poorer economic capital were more likely to feel depressed, and younger college students with higher academic stress were more likely to feel lonely. The results of t-test analyses indicated that quarantine affected students’ time and type of study turning to online studies and to moderate physical activities. The present study’s findings add to the existing literature and support the development of new measures to support students, both financially as well as psychologically.