Despite its benefits for people living with HIV/AIDS (PLWHA), home-based care (HBC) may have negative effects on caregivers. Caregivers experience high levels of burden and may be targets of HIV-related prejudice and discrimination. In this cross-sectional survey of 358 caregivers from five hospices across KwaZulu-Natal, South Africa, 49 (13.7%) caregivers personally experienced discrimination as a result of caring for PLWHA. One hundred and seventy (47.5%) marked one or more items on the HIV stigma scale. Eighty-eight percent had low to moderate levels of caregiver burden. People with higher level of burden and higher income were more likely to hold stigmatizing beliefs. Caregivers with the following characteristics: support from a nurse, support from community careworker, HIV stigmatizing beliefs, and personal experience of discrimination as result of caring for PLWHA and low caregiver burden, had more than twice the odds of wanting to care for another PLWA in the future. Overall, caregivers in HBC experience low level of severe caregiver burden. The support offered to caregivers from the hospice and relatively low levels of discrimination encourage expansion of HBC programs for PLWHA.