Screening measures for depression developed in high-income countries have not always demonstrated strong psychometric properties in South Africa and with people living with HIV (PLWH). The present study explored the psychometric properties of the 16-item South African Depression Scale (SADS) comprised of idioms of distress specific to isiXhosa culture in PLWH. The SADS was administered to 137 Xhosa-speaking PLWH who met diagnostic criteria for major depressive disorder (MDD) together with the Hamilton Depression Scale (HAM-D) and the Center for Epidemiological Studies Depression Scale (CES-D). We conducted exploratory factor analysis, correlation, and reliability statistics. Four factors of the SADS emerged: Sadness, lethargy/burdened, anhedonia/withdrawal, and cognitive/somatic. All factors correlated significantly with the HAM-D and CES-D. Internal consistency of the overall measure was high (α =.89). The SADS promises to be a robust measure of depression in isiXhosa-speaking PLWH in South Africa likely due to the inclusion of local idioms of distress.