To examine HIV service interruptions during the COIVD-19 outbreak in South Carolina (SC) and identify geospatial and socioeconomic correlates of such interruptions, we collected qualitative, geospatial, and quantitative data from 27 Ryan White HIV clinics in SC in March, 2020. HIV service interruptions were categorized (none, minimal, partial, and complete interruption) and analyzed for geospatial heterogeneity. Nearly 56% of the HIV clinics were partially interrupted and 26% were completely closed. Geospatial heterogeneity of service interruption existed but did not exactly overlap with the geospatial pattern of COVID-19 outbreak. The percentage of uninsured in the service catchment areas was significantly correlated with HIV service interruption (F = 3.987, P = .02). This mixed-method study demonstrated the disparity of HIV service interruptions in the COVID-19 in SC and suggested a contribution of existing socioeconomic gaps to this disparity. These findings may inform the resources allocation and future strategies to respond to public health emergencies.