Most vulnerable individuals are particularly affected by the COVID-19 pandemic. This study takes place in a large city in France. The aim of this study is to describe the mobility of the homeless population at the beginning of the health crisis and to analyze its impact in terms of COVID-19 prevalence. From June to August 2020 and September to December 2020, 1272 homeless people were invited to be tested for SARS-CoV-2 antibodies and virus and complete questionnaires. Our data show that homeless populations are sociologically different depending on where they live. We show that people that were living on the street were most likely to be relocated to emergency shelters than other inhabitants. Some neighborhoods are points of attraction for homeless people in the city while others emptied during the health crisis, which had consequences for virus circulation. People with a greater number of different dwellings reported became more infected. This first study of the mobility and epidemiology of homeless people in the time of the pandemic provides unique information about mobility mapping, sociological factors of this mobility, mobility at different scales, and epidemiological consequences. We suggest that homeless policies need to be radically transformed since the actual model exposes people to infection in emergency.