People experiencing homelessness (PEH) are at disproportionate risk of becoming infected and having severe illness from coronavirus disease 2019 (COVID-19), especially when residing in congregate settings like homeless shelters. Behavioral health problems related to substance use disorder (SUD) and severe mental illness (SMI) may have created additional challenges for PEH to practice prevention measures like mask wearing, physical distancing, handwashing, and quarantine and isolation. The study objective was to understand the perceived barriers PEH face regarding COVID-19 non-pharmaceutical prevention strategies and identify recommendations for overcoming barriers. From August-October 2020, qualitative phone interviews with 50 purposively selected behavioral health professionals across the United States serving PEH with SUD or SMI were conducted. Professionals described that PEH faced barriers to prevention that were structural (e.g., access to necessary resources), behavioral (related to SUD or SMI), or related to the priority of other needs. Recommendations to overcome these barriers included providing free prevention resources (e.g., masks and hand sanitizer), providing education about importance of prevention strategies, and prioritizing access to stable housing. Interviews took place before COVID-19 vaccines were available, so barriers to vaccination are not included in this paper. Findings can help support tailored approaches during COVID-19 and future public health threats.