BACKGROUND: Environmental quality of life (QoL) assesses individually perceived factors such as physical safety and security, accessibility, quality of healthcare, and physical environment. These factors are particularly relevant in the context of sex work and HIV, where stigma has been identified as an important barrier across several prevention and treatment domains. This study aims to examine the association between different types of HIV- and sex work-related stigmas and environmental QoL among female sex workers (FSW) living with HIV in Durban, South Africa. METHODS: We conducted cross-sectional analyses using baseline data from the Siyaphambili randomized controlled trial. FSW who reported sex work as their primary source of income and had been diagnosed with HIV for ≥ 6 months were enrolled from June 2018-March 2020, in eThekwini, South Africa. We evaluated the association between environmental QoL, dichotomizing the environmental domain score collected by the WHO Quality of Life HIV Brief (WHOQOL-HIV BREF) questionnaire at the median, and stigma using modified robust Poisson regression models. Five stigma subscales were assessed: sex work-related (anticipated, enacted, or internalized stigma) and HIV-related (anticipated or enacted stigma). RESULTS: Among 1373 FSW, the median environmental QoL was 10.5 out of 20 [IQR: 9.0-12.5; range 4.0-19.0], while the median overall QoL was 3 out of 5 [IQR: 2-4; range 1-5]. One-third of FSW (n = 456) fell above the median environmental QoL score, while 67% were above the median overall QoL (n = 917). Reporting anticipated sex work stigma was associated with lower environmental QoL (adjusted prevalence ratio [aPR] 0.74 [95% CI 0.61, 0.90]), as was severe internalized sex work stigma (aPR: 0.64, 95% CI 0.48, 0.86). Reporting enacted HIV stigma versus none was similarly associated with lower environmental QoL (aPR: 0.65, 95% CI 0.49, 0.87). Enacted sex work stigma and anticipated HIV stigma were not statistically associated with environmental QoL. CONCLUSIONS: This study highlights the need to consider the impact of multiple stigmas on FSW's non-HIV related clinical outcomes, including safety and physical well-being. Moreover, these results suggest that addressing underlying structural risks may support the impact of more proximal HIV prevention and treatment interventions. Trial registration NCT03500172 (April 17, 2018).