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Background: Focusing on the Meta region in Colombia, we investigated the relationship between mental health, the COVID-19 pandemic, and social determinants of health influenced by over five decades of civil conflict. We studied the post-2016 peace agreement trends in mental health for the population of Meta, before and after the local onset of the pandemic. Method: We conducted three rounds of a longitudinal health survey in years 2018 with N = 1309 (Women = 709; Men = 600); 2019 with N = 1106 (Women = 597; Men = 509); and 2020 with N = 905 (Women = 499; Men = 406). We measured mental health through the Self-Report Questionnaire (SRQ-20), investigating population trends in the average SRQ score and SRQ-positive frequency (SRQ + , indicating positive tendency towards experiencing mental health disorders). Results: Between 2018 and 2020, there were reductions in the mean SRQ-20 score by 1.74 points (95% CI -2.30 to -1.18) and in SRQ + frequency by 15 percentage points (95% CI -21.0 to -9.0) for the Meta population. Yet specific subgroups have become more vulnerable to mental illness during the pandemic, for example older age groups (e.g., increase in mean SRQ score among over 60 s by 2.49 points, 95% CI 0.51 to 4.46) and people living with children younger than five years-old (e.g., increase in mean SRQ score by 0.64 points, 95% CI 0.07 to 1.20). Increased mental health vulnerability among specific subgroups may be related to differences in the likelihood of knowing people who tested positive for COVID-19 or died from itf having been in quarantine. Conclusion: Our findings support the importance of public policies in Colombia (and other low- and middle-income countries) that address the social determinants of mental illness whose influence was likely exacerbated by the pandemic, including persistent job insecurity leading to work and financial pressures, and inadequate support networks for isolated individuals and vulnerable caregivers. [ABSTRACT FROM AUTHOR]