COVID-19 has disproportionally affected underrepresented minorities (URM) and low-income immigrants in the United States. The aim of the study is to examine the underlying vulnerabilities of Mexican immigrants in New York City (NYC) and Los Angeles (LA), its correspondence with area-level COVID-19 morbidity and mortality, and to document the role of trusted and culturally sensitive services offered during the pandemic through the Ventanillas de Salud (i.e. VDS, Health Windows) program. The study uses a mixed-methods approach including a cross-sectional survey of Mexican immigrants in LA and NYC collected in the Mexican Consulates at the onset of the pandemic, complemented with a georeferencing analysis and key informant interviews. Data suggested an increased vulnerability to COVID-19 given participants reported health status, health care profile and place of residence, which coincided with the georeferencing analysis. The key informant interviews confirmed the vulnerability of this population and the supporting role of VDS in helping immigrants navigate health systems and disseminate health information. Mexican immigrants had an increased vulnerability to COVID-19 at the individual, geographic and systemic levels. Trusted and culturally sensitive services are needed to overcome some of the barriers and risk factors that increase the vulnerability of URM and immigrant populations to COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10903-021-01283-8.