The increasing cases of HIV/AIDS have led to an increase in the number of children whose parents have died of HIV/AIDS. They are the AIDS Orphan, and their developmental needs are taken care of by either their next of kin or formal institutional caregiver after both parent's death. The inaccurate information about HIV/AIDS leads to these children being stigmatized. Previous studies have less focus on the formal institutional caregiver, particularly their acceptance of the AIDS Orphan. This study was conducted to measure the relationship between the caregivers' knowledge of HIV/AIDS and the stigma towards HIV/AIDS children who live in shelter homes. This study applied a quantitative data analysis method and carried out a survey design cross-sectionally in seven shelter homes. A total of 140 caregivers were purposively selected to participate in the study. Data were collected using a questionnaire taken from the HIV Knowledge Questionnaire (HIV-KQ-18), Measuring The Degree of HIVrelated Stigma and Discrimination in Health Facilities and Providers, and the Manual of Measuring HIV Stigma and Discrimination among Health Facility Staff Questionnaire. The results indicated that 83.6% of respondents have moderate knowledge about HIV/AIDS, and 80.7% of respondents had a moderate level of stigma towards HIV children.. Findings suggesta significant correlation between knowledge of HIV/AIDS and stigma (r = .269, k <001). The lack of knowledge about HIV transmission leads to stigma among caregivers. The results of this study emphasize the importance of having a precise knowledge of the HIV/AIDS medium of transmission, prevention, and treatment in order for the caregivers to manage the AIDS Orphan without discrimination. The study also highlights the implications for recognizing measures to reduce stigma among caregivers as it reflects the quality of health and psychosocial development of HIV/AIDS children under their care.