Given the high prevalence of HIV in South Africa and co-morbid mental disorders in people living with HIV/AIDs (PLWHA) we sought to validate a brief screening tool in primary HIV care. Methods: 366 PLWHA were recruited prior to combination anti-retroviral treatment (CART) initiation from two primary health HIV clinics. A mental health nurse administered a socio-demographic questionnaire and the Mini Neuropsychiatric Interview (MINI) and a lay counsellor administered the Substance and Mental Illness Symptom Screener (SAMISS). Results: Using the MINI, 17 % of participants were identified with either depression, anxiety disorders or adjustment disorder and 18 % with substance or alcohol abuse/dependence. The sensitivity and specificity of the SAMISS was 94 % (95 % CI: 88–98 %) and 58 % (95 % CI: 52–65 %) respectively, with the alcohol component (sensitivity: 94 %; specificity: 85 %) performing better than the mental illness component of the SAMISS (sensitivity: 97 %; specificity: 60 %). The specificity of the tool improved when the cut-off for the mental illness component was increased. Conclusion: The SAMISS may provide a useful first tier screening tool for common mental disorders in primary care for PLWHA.