Background Quarantine often is an unpleasant experience. The aim of this study is to explore the degree of psychological distress in terms of-Depression, Anxiety and Stress among the adult population in India during the strict 21 days mandatory lockdown. We hypothesize that quantification of psychological impact of current situation will help us to modify the policies and implementation strategies. This assessment might also help in future to keep targeted services in place, to cope up with the psychological distress of the quarantined population. Method A cross sectional survey design was adopted to assess the psychological state of general population in India, during the COVID-19 mandatory lockdown period, with the help of a validated questionnaire. Findings The reported prevalence of depression was around 30.5%, which was the highest among the variables of psychological health. Anxiety was reported by 22.4%, followed by stress which was seen in 10.8% of respondents. In the third week the incidence of depression (37.8% versus 23.4%; p<0.001), anxiety (26.6% versus 18.2%; p<0.001) and stress (12.2% versus 9.3%; p<0.045) was reported to be significantly higher as compared to second week. Interpretation Our results suggest a progressively detrimental impact of lockdown on various aspects of psychological health. We noticed around eight to ten fold increase in the prevalence of depression (30.5%) and anxiety (22.4%) during lockdown, as compared to baseline statistics in Indian population (3 1-3 6% for depressive disorders and 3 0-3 5% for anxiety disorders). © 2020 Pandey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.