With an eye to health equity and community engagement in the context of the initial COVID-19 vaccine roll-out, the COVID-19-related concerns of the Latinx (Hispanic/Latino) community in southern San Diego (California, USA) were examined using 42 rapid, ethnographically-informed interviews and two focus groups conducted in early-mid 2021. An anthropologically oriented qualitative analysis delimited the cultural standpoint summarized as aguantarismo, which celebrates human durability in the face of socioeconomic hardship and the capacity to abide daily life’s challenges without complaint. After characterizing aguantarismo, its role in both undermining and supporting vaccine uptake is explored. To avoid diverting attention from the structural factors underlying health inequities, the analysis deploys the theoretical framework of critical medical anthropology, highlighting inequities that gain expression in aguantarismo, and the indifference toward vaccination that it can support. In placing critical medical anthropology into conversation with the cultural values approach to public health, the analysis sheds new light on the diversity of human strategies for coping with infectious disease and uncovers new possibilities for effective vaccination promotion. Findings will be useful to public health experts seeking to convert non-vaccinators and optimize booster and pediatric COVID-19 vaccine communications. They will also contribute to the literature on cultural values in relation to Hispanic/Latino or border health more broadly, both by confirming the vital flexibility of cultural standpoints like aguantarismo and by documenting in situ what is to the social science and health literature, albeit not to cultural participants, a novel constellation.