American Indian or Alaska Native (AI/AN) persons across the United States face substantial health disparities, including a disproportionately higher incidence of COVID-19 (1,2). AI/AN persons living in Alaska also face serious health and health care challenges, including access to care because 90% of the state’s land area is inaccessible by road (3), and approximately one half of the state’s AI/AN population (AI/AN race alone or in combination with another race) live in remote rural areas (4). To examine the extent of COVID-19-associated disparities among AI/AN persons living in Alaska, a retrospective analysis of COVID-19 cases reported to the Alaska Department of Health and Social Services (AKDHSS) during March 12, 2020-December 31, 2021, was conducted. The age-adjusted COVID-19 incidence among AI/AN persons was 26,583 per 100,000 standard population, approximately twice the rate among White persons living in Alaska (11,935). The age-adjusted COVID-19-associated hospitalization rate among AI/AN persons was 742 per 100,000, nearly three times the rate among White persons (273) (rate ratio [RR] = 2.72). The age-adjusted COVID-19-related mortality rate among AI/AN persons was 297 per 100,000, approximately three times that among White persons (104; RR = 2.86). Culturally competent public health efforts that are designed in collaboration with AI/AN persons and communities, including support for vaccination and other proven COVID-19 prevention strategies, are critical to reducing COVID-19-associated disparities among AI/AN persons in Alaska.