Given the existing evidence linking parental depression with infant and early child development, our aim was to describe the burden of mental health disorders among caregivers of young children aged 4-6 years living in an environment of poverty and high HIV seroprevalence. We analyzed baseline data from an epidemiologic study of the health and psychosocial needs of preschool-aged children. Primary caregivers of index children recruited from a household survey were screened for common mental disorders using the Client Diagnostic Questionnaire (CDQ). Sociodemographic, HIV and general health surveys were also conducted. Many caregivers (449/1,434; 31.3 %) screened positive for at least one psychiatric disorder on the CDQ, with post-traumatic-stress-disorder being the most common. Caregivers who screened positive for any disorder were more likely to be older, to have no individual sources of income and to have less formal education. Presence of a disorder was also significantly associated with lower employment levels within the household and death of a young child within the household. Known HIV-infected caregivers were more likely to have any mood disorder than caregivers who previously tested negative. The data support the need for mental health treatment interventions in South Africa, particularly interventions directed at PTSD and depression, and that take into account the high burden of poverty, HIV and childhood mortality. Given the limited formal mental health structure in South Africa to address these highly prevalent disorders; community-based mental health supports, available through decentralized health systems many be critical to delivering accessible interventions.