Introduction: Closures and reductions in capacity of select health and social services in response to the COVID-19 pandemic may have placed people who use drugs (PWUD) at a disproportionately increased risk for experiencing harms, and resulted in critical treatment disruptions. We conducted the current national study among a cohort of PWUD to understand how COVID-19 has affected service access, including any significant impacts PWUD may have experienced. Results will contribute to the evidence base for informing future pandemic and public health policy planning for vulnerable populations. Methods: The project involved qualitative telephone-based interviews with 196 adult (aged 18+) PWUD from across Canada. Eligibility criteria included daily or weekly use of psychoactive substance(s), and/or current enrollment in opioid agonist treatment (OAT). Data collection took place between May and July 2020. Data underwent thematic analyses, and common themes informed the results. Results: Most participants experienced detrimental service access issues and treatment disruptions during COVID-19, including reduced access to harm reduction services, OAT, withdrawal management and treatment services, medical professionals (e.g., addictions and mental health counseling), shelters/housing, and food banks. Positive impacts included greater access to OAT take-home ‘carries’ and prescription deliveries. Decreases in service capacity resulted in increased health issues and risky substance use behaviors among PWUD, such as unaccompanied substance use, sharing/re-use of supplies, and overdose events. Conclusions: Reductions in the accessibility of critical services PWUD rely on during COVID-19 has increased existent substance use and health issues among PWUD, while decreasing their ability to mitigate risks related to substance use. Thus, the expansion of the depth and breadth of support options is crucial. Services must remain open and flexible to the unique needs of PWUD during COVID-19, while novel and effective adaptations and interventions should remain available and accessible post-COVID-19.