Caregivers of children living with HIV/AIDS (CLWHA) face unique challenges due to disease-related stigma and discrimination, isolation from society, financial constraints, grief and mortality of loved one. A descriptive cross-sectional study was conducted at Udupi ART centre to assess the caregiver burden, psychological distress and their associated factors among the caregivers of CLWHA in Udupi District. The convenience sampling technique was used to collect the data from 171 caregivers and analysed with the help of SPSS version 15.0. Majority of caregivers were female (64.9%) with mean age of 38.1 +/- 9.6 years. About 64.3% caregivers were HIV-positive and 63.2% were biological parents of CLWHA. Mild-to-severe caregiver burden on Zarit Burden Inventory (ZBI) was reported among 84.8% of caregivers, and mild-to-severe psychological distress on General Health Questionnaire (GHQ-12) was reported among 49.7% caregivers. Relationship with child was found to be a significant predictor of caregiver burden as compared to other relatives/foster (P<0.001). Relationship with child (P 0.004), Alcohol use (P 0.008) and Schooling of children (P 0.049) were reported as significant predictors of psychological distress. Study concludes that caregiver burden and psychological distress were high among caregivers of CLWHA. Psychological problems of caregivers need to be addressed and integrated along with the clinical care of HIV-infected children at ART centres.