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Purpose: To study the associations between physical activity (PA), cardiorespiratory fitness (CRF), and health-related quality of life (HRQoL) in black African women from a low socioeconomic community in South Africa.Methods: Black African women (n = 146) aged 35-75 years from a low socioeconomic community in South Africa participated in this study. We measured PA levels via ActiHeart® accelerometers, and CRF by measuring peak oxygen consumption (V̇O2 peak). HRQoL was assessed once with the SF-8 Health Survey (SF-8). Participants were classified into groups based on age, moderate to vigorous PA (MVPA), and V̇O2 peak. Logistic regressions were used to compare the odds of having total HRQoL component scores above reported norms across PA and fitness groups. Two multiple linear regression models were developed using physical component summary (PCS) and mental component summary (MCS) as response variables respectively.Results: V̇O2 peak and MVPA varied considerably across the sample and declined with increasing age. Participants in higher quartiles of MVPA and CRF showed trends to higher PCS scores. For CRF these trends were statistically significant, and persisted after adjustment for age and other possible confounders (p = 0.036). PCS was significantly associated with age, relative V̇O2 peak, and income (all p < 0.05), while MCS was associated with income (p = 0.028).Conclusions: CRF is the most significant predictor, together with age and income, on the PCS of the HRQoL among black African women. We recommend that when seeking improvements in HRQoL, interventions should focus on improving CRF, particularly V̇O2 peak. [ABSTRACT FROM AUTHOR]