This article seeks to understand how and why certain locations are excluded from or seen as foreclosed as places of innovation and knowledge production in health research and practice. Rooted in several years of collaborative ethnographic research in Mississippi, we develop this conceptual framework to understand the persistence of – and often ineffective response to – racialized and classed health disparities. We define our concept of epistemic prejudice as a structural inability or resistance to seeing certain places, bodies, and locations as capable of knowledge production and innovation. The history of the community health center movement, paired with the portrayal of Mississippi in contemporary media representations, helps us develop our concept. We use an interface ethnography method as Mississippi scholars to demonstrate the importance of this model of research in understanding persistent inequality in places of ‘lack’, noting that the challenges of addressing health problems in Mississippi stem in part from epistemic prejudice of scholars, health care practitioners, and policy-makers. Epistemic prejudice has broader implications for how global health initiatives are implemented, how postcolonial frameworks still shape knowledge production, and how knowledge is generated and taken as authoritative.