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The goal of this study was to establish effective, culturally appropriate strategies to enhance participation of American Indian/Alaska Native (AI/AN) communities in prevention and treatment of COVID-19, including vaccine uptake. Thirteen Community Health Representatives (CHRs) from three Arizona Native nations tailored education materials to each community. CHRs delivered the intervention to over 160 community members and administered a pre-posttest to assess trusted sources of information, knowledge, and self-efficacy and intention regarding COVID-19 vaccines. Based on pre-posttest results, doctors/healthcare providers and CHRs were the most trusted health messengers for COVID-19 information; contacts on social media, the state and federal governments, and mainstream news were among the least trusted. Almost two-thirds of respondents felt the education session was relevant to their community and culture, and more than half reported using the education materials to talk to a family member or friend about getting vaccinated. About 67% trusted the COVID-19 information provided and 74% trusted the CHR providing the information. Culturally and locally relevant COVID-19 vaccine information was welcomed and used by community members to advocate for vaccination. The materials and education provided by CHRs were viewed as helpful and emphasized the trust and influence CHRs have in their communities.