Trans women engaged in sex work live at the intersections of discrimination against sex workers, women and transgender people. Dominant public health approaches have constructed trans women in sex work as a group at high risk of HIV infection. This study employed localocentricity, situated within a cultured-centred approach, as a theoretical framework to document health narratives among 29 trans women who had knowledge of or experience in sex work. This theoretical framing draws attention to the articulations between health and illness expressed by trans women in sex work in USA. Research participants emphasised how their health was affected by extreme socio-political-cultural marginalisation as well as medical poverty and mental health issues.