Background: The emotional impacts of witnessing and responding to overdose and overdose-related deaths have been largely overlooked during the drug toxicity overdose crisis in North America. Scarce research has analyzed these impacts on the health and well-being of harm reduction workers, and the broader determinants of harm reduction work. Our study investigates the experiences and impacts of witnessing and responding to frequent and escalating rates of overdose on harm reduction workers in Toronto, Canada., Methods: Using semi-structured interviews, 11 harm reduction workers recruited from harm reduction programs with supervised consumption services in Toronto, Canada, explored experiences with and reactions to overdose in both their professional and personal lives. They also provided insights on supports necessary to help people cope with overdose-related loss. We used thematic analysis to develop an initial coding framework, subsequent iterations of codes and emergent themes., Results: Results revealed that harm reductions workers experienced physical, emotional, and social effects from overdose-related loss and grief. While some effects were due to the toll of overdose response and grief from overdose-related losses, they were exacerbated by the lack of political response to the scale of the drug toxicity overdose crisis and the broader socio-economic-political environment of chronic underfunding for harm reduction services. Harm reduction workers described the lack of appropriate workplace supports for trauma from repeated overdose response and overdose-related loss, alongside non-standard work arrangements that resulted in a lack of adequate compensation or access to benefits., Conclusions: Our study highlights opportunities for organizational practices that better support harm reduction workers, including formal emotional supports and community-based supportive care services. Improvement to the socio-economic-political determinants of work such as adequate compensation and access to full benefit packages are also needed in the harm reduction sector for all workers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)