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Many studies have shown that COVID-19 caused many problems in mental health. This paper presents the results of the Cyprus sample, part of the global initiative named "The Collaborative Outcomes Study on Health and Functioning during Infection Times" (COH-FIT). Methods: The study took place from April 2019 to January 2022, using the Greek version of the online standard COH-FIT questionnaire on 917 Cypriot adults. Weighted t-tests were applied to test the differences between pre-pandemic and intra-pandemic scores using the anesrake package. Results: Participant responses indicated a significant negative impact of the pandemic on measures of mental health (−7.55; 95% CI: −9.01 to −6.07), with worsening in the scores for anxiety (12.05; 95% CI: 9.33 to 14.77), well-being (−11.06; 95% CI: −12.69 to −9.45) and depression (4.60; 95% CI: 2.06 to 7.14). Similar negative effects were observed for feelings of anger (12.92; 95% CI: 10.54 to 15.29), helplessness (9.66; 95% CI: 7.25 to 12.07), fear (22.25; 95% CI: 19.25 to 25.26), and loneliness (12.52; 95% CI: 9.94 to15.11). Increased use of social media (0.89; 95% CI: 0.71 to 1.09), internet (0.86; 95% CI: 0.67 to 1.04), and substance consumption (0.06; 95% CI: 0.00 to 0.11) were reported, along with a significant decrease in physical health (−3.45; 95% CI: −4.59 to −2.32), self-care (−7.10; 95% CI: −9.00 to −5.20), and social function (−11.27; 95% CI: −13.19 to −9.35), including support (−0.72; 95% CI: −1.09 to −0.34) and family function (−7.97; 95% CI: −9.90 to −6.05). Conclusions: The COVID-19 pandemic significantly affected the daily life and emotional well-being of Cypriots. Identifying factors that influence vulnerability and resilience is essential to prioritize mental health support and address the long-term effects of the pandemic. [ABSTRACT FROM AUTHOR]