Background: Accumulating evidence suggests that the COVID-19 pandemic has negatively affected global mental health and well-being. However, the impact amongst homeless persons has not been fully evaluated. The ECHO study reports factors associated with depression amongst the homeless population living in shelters in France during the spring of 2020. Methods: Interview data were collected from 527 participants living in temporary and/or emergency accommodation following France's first lockdown (02/05/20-07/06/20), in the metropolitan regions of Paris (74%), Lyon (19%) and Strasbourg (7%). Interviews were conducted in French, English, or with interpreters (33% of participants, ~20 languages). Presence of depression was ascertained using the Patient Health Questionnaire (PHQ-9). Results: Amongst ECHO study participants, 30% had symptoms of moderate to severe depression (PHQ-9 ≥ 10). Multivariate analysis revealed depression to be associated with being female (aOR: 2.15; CI: 1.26-3.69), single (aOR: 1.60; CI: 1.01-2.52), chronically ill (aOR: 2.32; CI: 1.43: 3.78), facing food insecurity (aOR: 2.12; CI: 1.40-3.22) and participants' region of origin. Persons born African and Eastern Mediterranean regions showed higher levels of depression (30-33% of participants) than those migrating from other European countries (14%). Reduced rates of depression were observed amongst participants aged 30-49 (aOR: 0.60; CI: 0.38-0.95) and over 50 (aOR: 0.28; CI: 0.13-0.64), compared to 18-29-year-olds. Limitations: These data are cross-sectional, only providing information on a given moment in time. Conclusions: Our results indicate high levels of depression amongst homeless persons during the COVID-19 pandemic. Predicted future instability and economic repercussions could particularly impact the mental health of this vulnerable group.