Background To inform preparedness and population health action, we need to understand the effects of COVID-19 on health inequities. In this study, we assess the impact of COVID-19 on opioid toxicity deaths among people who experience incarceration compared to others in the general population in Ontario, Canada. Methods We conducted a retrospective cohort study for the period of January 1, 2015 to December 31, 2020. We accessed and linked coronial data on all opioid toxicity deaths in Ontario with correctional data for people aged 18 years and older who were incarcerated in a provincial correctional facility. We used data from the Statistics Canada Census to calculate whole population rates. We used an interrupted time series design and segmented regression to assess for change in the level or rate of increase in deaths due to opioid toxicity coinciding with the COVID-19 pandemic. We compared the impact of COVID-19 on the opioid toxicity death rates for people exposed and not exposed to incarceration. Results Rates of opioid toxicity death increased with a linear positive slope in both persons exposed to incarceration and those not exposed over the study period. The start of COVID-19 measures coincided with a marked upward shift in the trend lines with modification of the effect of COVID-19 by both sex and exposure to incarceration. For persons exposed to incarceration, the risk ratio (RR) was 1.50 (95%CI 1.35–1.69) for males and 1.21 (95%CI 1.06–1.42) for females, and for persons not exposed to incarceration, the RR was 1.25 (95%CI 1.13–1.38) for males and not significant for females. Conclusions COVID-19 substantially exacerbated the risk of opioid toxicity death, impacting males and females who experienced incarceration more than those who had not, with an immediate stepwise increase in risk but no change in the rate of increase of risk over time. Public health work, including pandemic preparedness, should consider the specific needs and circumstances of people who experience incarceration.