Health-related quality of life (HRQOL) is an important and frequently used patient-reported outcome in health research. However, little qualitative research exists in this field in South Africa. This study was set in Khayelitsha, one of the largest informal settlements in South Africa, where the burden of HIV and tuberculosis (TB) co-infection are amongst the highest in the world and significantly affect HRQOL. To explore the experience of HRQOL among patients living with HIV-associated TB. We conducted sixteen interviews with male (n = 10) and female (n = 6) adult participants (ages 24-56; median age 35) to explore their HRQOL living with HIV-associated TB, related treatment and how this impacted on life domains they considered relevant for HRQOL. We used thematic analysis to analyse data, using both an inductive and deductive analysis using an interpretive phenomenological approach (IPA). Experiences of HRQOL were identified along the predominantly emerging themes of physical, social, and mental aspects of HRQOL. Identified sub-themes included well-being, loss of strength, and self-care for the physical domain; usual activities and stigma for the social domain; concerns and coping for the mental domain. The findings illustrate that HRQOL domains are interconnected through social experience. The social experience of HRQOL was identified as the common denominator connecting all domains, around which HRQOL revolved for these participants. HRQOL is experienced socially. The interpersonal connections patients have with significant others present as key to high HRQOL among patients living with HIV-associated TB. This study adds to the existing literature of HRQOL and examines HRQOL using IPA which may help to inform future interventions to improve HRQOL among HIV/TB patients.