Background. The identification of general population groups particularly vulnerable to the impact of COVID-19 lockdown measures on mental health and the development of healthcare policies are priority challenges in the current and future pandemics. Objective. To identify the personal and social determinants of the impact of COVID-19 lockdown measures on mental health in a large sample of the Colombian population. Design. In this cross-sectional study, an anonymous online survey was answered by 18,061 participants from the general population residing in Colombia during the first wave of the COVID-19 outbreak (from May 20th to June 20th, 2020). Main outcome measures. Symptoms of depression, anxiety, and somatisation were measured using the Patient Health Questionnaire (PHQ-2), Generalized Anxiety Disorder Scale (GAD-2), and Somatic Symptom Questionnaire (SSQ-5), respectively. Results. Overall, 35% of participants showed symptoms of depression, 29% of anxiety, and 31% of somatization. According to the analysis of social determinants of health, the most affected groups were people with low incomes, students, and young adults. Specifically, low-income young females were the most at-risk population group. Conclusion. These findings show how the lockdown measures impacted on the general population's mental health in Colombia and highlights some social risk factors in health.