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Social inequities compromise health-related quality of life (HR-QoL) among women living with HIV (WLWH). Little is known about health impacts of intersecting stigma based on HIV status, race and gender among WLWH or potential mechanisms to promote HR-QoL. We tested pathways from multiple types of stigma (HIV-related, racial, gender) to physical and mental HR-QoL utilizing baseline survey data from a national cohort of WLWH in Canada (2013–2015). Structural equation modeling was conducted using maximum likelihood estimation methods to test the direct effects of HIV-related stigma, racial discrimination, and gender discrimination on HR-QoL and indirect effects via social support and economic insecurity, adjusting for socio-demographic factors. Among 1425 WLWH (median age: 43 years [IQR = 35–50]), HIV-related stigma and gender discrimination had significant direct effects on mental HR-QoL …