Background and Objectives: Despite increasing drug use in rural communities, potentially life-saving harm reduction interventions, such as needle exchange programs (NEPs), remain underutilized. Religion is an integral component of the rural culture that has been shown to influence health, yet no studies to date have explored rural faith leaders' perceptions of harm reduction strategies.Methods: An online cross-sectional survey was conducted among rural faith leaders (n = 133) in the rural Illinois Delta Region.Results: While most of the respondents felt that drug abuse was an issue in their communities, support was mixed regarding whether they were in favor of NEPs with the majority of respondents having never heard of an NEP before this survey. While the majority believed that NEPs would help decrease bloodborne disease transmission, it was also perceived that NEPs would increase drug use. Significant differences in perceptions based on race, marital status, and political party also exist. Conclusion and ScientificSignificance: Congruent with previous harm reduction literature, many rural faith leaders have varied perceptions of NEPs. Rural faith leaders could benefit from education about NEPs, including the possible positive and negative impacts they can have on the community. Future studies should explore contextual differences among rural faith leaders. To date, no studies have examined faith-based organizations' perceptions of NEPs. The findings have the potential to increase the current body of knowledge and provide data to support recommendations for engaging faith-based organizations in behavioral health service delivery.