Background: The increased contamination of illicit drugs with fentanyl in the United States drug market has contributed to escalating mortality from drug overdose. Leisure and hospitality service industry workers are encountering opioid-triggered overdoses in their workplaces, such as restaurants and bars. Consequently, this increases the need for overdose education and naloxone distribution (OEND) training, which has been limited. We aimed to describe the experiences among service industry workers encountering an overdose in their workplace. Methods: We conducted in-depth qualitative interviews with service industry workers in Little Five Points (L5P), Atlanta, between October 2019 and April 2020 and triangulated methods with participant observations and fieldwork. Purposive criterion sampling methods were applied to recruit from different establishments in the L5P commercial district, which comprised restaurants, bars, retail shops, and theaters. After an initial seed sample was identified by engaging key stakeholders during fieldwork (business owners, managers, and the business association), a snowball sample followed for a final sample of N = 15. To contextualize the local population of harm reduction workers, people who use drugs and/or obtain safer drug consumption supplies in L5P (sterile syringes, safer using kits, naloxone), and service industry workers and their customers in L5P, the first author volunteered with an Atlanta syringe services program from October 2019 to April 2020. The first author conducted participant observations during the syringe exchange program and field notes were taken during observation (44 hours). This engagement ensured a rich, thick description. We used a pragmatic approach to thematic data analysis for this study. Data were analyzed iteratively and inductively from interviews and observations. Two independent researchers reviewed transcripts to identify passages in the data related to the question of interest. The passages were contextualized within the full data set independently to understand the relationships in developing a theory of what was commonly occurring across participants’ experiences, and these relationships led to emerging salient themes regarding encountering an opioid overdose at work. Results: One salient theme related to overdose response emerged with the service industry workers included fear of negative consequences of overdose response, specifically, fear of disease transmission from artifacts of drug use and overdose response, including the spread of blood-borne disease, violence, and exposure to unintentional overdose. When discussing drug use, participants’ beliefs about the potential for personal danger from drug use artifacts (syringes and discarded drugs) and violence were identified as barriers to opioid overdose responses. Conclusions/Implications for Occupational Health Practice: Our findings provide valuable insights for tailoring OEND training for service industry workers to confront fears associated with opioid overdose response in their places of work to decrease mortality from the opioid epidemic. Harm reduction approaches need to be sensitive to the places in which overdose occurs and who the overdose responder is likely to be, which requires appropriately tailoring OEND training for service industry workers.