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Objective: Understanding COVID-19-related mortality among the large population of people experiencing homelessness (PEH) in Los Angeles County (LA County) may inform public health policies to protect this vulnerable group. We investigated the impact of COVID-19 on PEH compared with the general population in LA County., Methods: We calculated crude COVID-19 mortality rates per 100 000 population and mortality rates adjusted for age, race, and sex/gender among PEH and compared them with the general population in LA County from March 1, 2020, through February 28, 2021., Results: Among adults aged ≥18 years, the crude mortality rate per 100 000 population among PEH was 20% higher than among the general LA County population (348.7 vs 287.6). After adjusting for age, the mortality rate among PEH was 570.7 per 100 000 population. PEH had nearly twice the risk of dying from COVID-19 as people in the general LA County population; PEH aged 18-29 years had almost 8 times the risk of dying compared with their peers in the general LA County population. PEH had a higher risk of mortality than the general population after adjusting for race (standardized mortality ratio [SMR] = 1.4; 95% CI, 1.2-1.6) and sex/gender (SMR = 1.3; 95% CI, 1.1-1.5)., Conclusions: A higher risk of COVID-19-related death among PEH compared with the general population indicates the need for public health policies and interventions to protect this vulnerable group.