This article takes a new direction in exploring HIV-related fatigue by adopting a qualitative interactionist approach. We analyse the social meanings attributed to fatigue among people living with HIV in France, the social gains and losses of its visibility and the social frames that condition its discursive and physical expression. The two-part methodology combines grounded theory analysis of 50 transcribed unstructured interviews conducted across France and participant observations within four HIV-related associations. Results reveal that the visibility of fatigue is in part dependent on the visibility of this stigmatized illness. The expression of fatigue is therefore closely linked with disclosure and concerns about HIV stigma. The degree to which HIV and HIV-related fatigue are rendered (in)visible also depends on structural factors including gender prescriptions, as well as context effects such as the type of social or 'care' relations involved in the social frame of interaction.