Context: Large numbers of US adults are vaccinated, but COVID-19 vaccine hesitancy remains high. Health centers funded by the Health Resources and Services Administration (HRSA) have played a major role in COVID-19 vaccinations and have the potential to vaccinate even larger numbers of people. Objective: To identify U.S. counties with low COVID-19 vaccination rates and high rates of vaccine hesitancy, explore the characteristics of these counties and health center presence in these areas, and identify priority health centers for targeted vaccine outreach. Study Design: Cross-sectional geospatial analysis of county-level COVID-19 vaccination rates and COVID-19 vaccination hesitancy. Bivariate Local Moran’s I using GeoDa software to identify clusters of counties with low COVID-19 vaccination rates and high rates of COVID-19 vaccine hesitancy. Geographic Information Systems (GIS) mapping to overlay health centers with county-level data. Setting or Dataset: U.S. counties; vaccine hesitancy data from U.S. Department of Health & Human Services Office of the Assistant Secretary for Planning and Evaluation (ASPE); vaccination rates from the Centers for Disease Control and Prevention (CDC); and data on Health Center Program awardees from the HRSA. Population studied: U.S. Counties (n=2,825) for which data on COVID-19 vaccination and COVID-19 vaccine hesitancy are available; and HRSA-funded health centers, excluding Puerto Rico and Pacific Islands (n=1,559). Outcome Measures: COVID-19 vaccine hesitancy and COVID-19 vaccination rates. Results: We identified 219 counties that are part of clusters of high rates of vaccine hesitancy and low COVID-19 vaccination rates. In general, these counties have higher rates of poverty, larger percentages of black and Hispanic populations, and are located in the Southeast (Alabama, Georgia) and West Virginia. Sixty health center awardees are located within these counties, serving almost 700,000 patients. Conclusions: While almost one-half of US adults have been vaccinated, younger adults have much lower rates of vaccination and large numbers are still unvaccinated. Further, vaccine rates vary by race and ethnicity, with less than one-fifth of Hispanic and black adults having been vaccinated. Targeting areas with high rates of vaccine hesitancy and low vaccination rates supports strategic planning, optimizes finite resources, and better assists health centers in creating culturally competent outreach addressing vaccine hesitancy.