In this population-based retrospective cohort study, changes in weekly rates of emergency department (ED) visits for drug overdoses were examined among individuals with a recent history of homelessness (IRHH) and their housed counterparts during the pre-pandemic, peak, and re-opening periods of the first wave of the COVID-19 pandemic, using corresponding weeks in 2019 as a historical control.

• Participants were 38,617 IRHH, 15,022,369 housed individuals, and 186,858 low-income housed individuals.

• Relative to housed individuals and matched housed individuals, IRHH had higher average rates of ED visits for drug overdoses between January and September 2020.

• All groups had a reduction in ED visits for drug overdoses by approximately 20% during the peak period (March 17 to June 16, 2020) compared with corresponding weeks in 2019.

• During the re-opening period (June 17 to September 26, 2020), significantly higher rates of ED visits for drug overdoses were observed among IRHH, matched housed individuals, and housed individuals relative to equivalent weeks in 2019.

• During the re-opening period of the COVID-19 pandemic, disproportionate increases in emergency department visits for drug overdoses were recorded for recently homeless individuals compared with housed people.