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Impacts of the COVID-19 pandemic on unregulated drug markets in North America have not been well characterized. We sought to estimate potential changes in the availability and retail price of unregulated drugs in Vancouver, Canada pre- vs. post-emergence of the COVID-19 pandemic. We used self-report data from two prospective cohorts of people who use drugs in Vancouver. While more research is needed to investigate reasons for the observed trends, the stagnant price amidst decreased availability for all drugs examined in this study (save cocaine) may reflect decreased purity/increased contamination of unregulated drugs following the beginning of the pandemic in our study setting. These findings may have implications for drug policy and practice approaches, particularly in regions where synthetic psychoactive substances are increasingly dominating the unregulated drug supply.