The study examines the trends in opioid-related deaths across nine Canadian provinces and territories from 2019 to 2021, focusing on the impact of the COVID-19 pandemic. Between 2019 and 2021, the annual number of opioid-related deaths increased from 3,007 to 6,222, with years of life lost (YLL) rising from 126,115 to 256,336. The highest YLL was observed among males (181,525 YLL) and individuals aged 30–39 years (87,045 YLL). The proportion of all deaths attributable to opioids increased significantly across all age groups, with the largest increases among those aged 30–39 years (50.3%) and 20–29 years (48.0%). The COVID-19 pandemic was associated with a significant increase in opioid-related deaths, particularly in provinces like Manitoba and Saskatchewan, where fentanyl-related deaths increased. The study highlights the urgent need for targeted harm reduction policies and programs to address the growing opioid crisis in Canada.The study examines the trends in opioid-related deaths across nine Canadian provinces and territories from 2019 to 2021, focusing on the impact of the COVID-19 pandemic. Between 2019 and 2021, the annual number of opioid-related deaths increased from 3,007 to 6,222, with years of life lost (YLL) rising from 126,115 to 256,336. The highest YLL was observed among males (181,525 YLL) and individuals aged 30–39 years (87,045 YLL). The proportion of all deaths attributable to opioids increased significantly across all age groups, with the largest increases among those aged 30–39 years (50.3%) and 20–29 years (48.0%). The COVID-19 pandemic was associated with a significant increase in opioid-related deaths, particularly in provinces like Manitoba and Saskatchewan, where fentanyl-related deaths increased. The study highlights the urgent need for targeted harm reduction policies and programs to address the growing opioid crisis in Canada.