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Purpose The COVID-19 outbreak escalated into a global pandemic, forcing governments around the world to impose measures affecting all aspects of life. Like other countries, Greece adopted social restriction, lockdowns, and quarantines to reduce transmission from person-to-person. This cross-sectional study investigated the impact of social restriction measures on mental health in a Greek adult sample. Method An online questionnaire collected data during the second national lockdown (February to May 2021). A total of 650 participants (M age: 33.13, 71.5% female) comprised the final sample. Results 21.3% of respondents reported moderate-to-extremely severe anxiety, 33% moderate-to-extremely severe depression, 31.8% moderate-to-severe stress, and 38% clinically significant trauma-related distress. Hierarchical linear regression analyses revealed that the strongest contributors to adverse mental health outcomes were being female, younger age, experiencing increases in verbal arguments at home, being separated from family and close friends, and being unable to afford enough or healthy food. Lastly, participants moved away from social support and into more individual strength and resilience-based coping strategies to cope with challenges. Conclusion These findings suggest that in addition to the detrimental effects on physical health, COVID-19 also imposed a heavy psychological burden on the population via forced social isolation, which, by design, increased not only physical distancing but also psychological distancing between people.