Objective: This study aimed to draw a general picture of the impact of the coronavirus dis-ease 2019 (COVID-19) pandemic on the life of higher-education students in Istanbul, with specific emphasis on the relationship between students’ social support systems, health-risk behaviors, and mental/academic well-being. Methods: A total of 2583 higher-education students from different fields of study par-ticipated in an online survey gathering information from several domains, including available social networks, support-seeking attitudes, substance use patterns, physical activity levels, academic stress, academic satisfaction, and psychological well-being during the pandemic. Results: Our findings pointed to major changes in students’ life circumstances and daily routines during COVID-19, including a significant decrease in contact with friends, over-all substance use, and physical activity as well as high levels of depression, academic stress, and academic dissatisfaction. Depressive symptoms were significantly predicted by the loneliness score (OR = 2.08, 95% CI = 1.88-2.29), female gender (OR = 1.65, 95% CI = 1.21-2.24), frequency of binge drinking (OR = 1.4, 95% CI = 1.06-1.86), and level of academic stress (OR = 1.15, 95% CI = 1.1-1.19), whereas the number of people to easily bor-row money from was found to be a protective factor against depression (OR = 0.95, 95% CI = 0.92-0.99). Conclusion: Our results highlight the need for higher-education institutions to take the appropriate social and mental health interventions, tailored to fit the specific require-ments of the COVID-19-related measures. © 2021 Institute of Electrical and Electronics Engineers Inc. All rights reserved.