Estimates indicate that HIV affected children are fifty times the number of infected children. These affected (not infected) children are under noticed by the policies in HIV related interventions even though they take more responsibility to take care of their infected family members. Methodology: Cross-sectional descriptive study was conducted with Children Affected by HIV/AIDS in 2014-15. Multistage sampling methodology was adopted to select the respondents. 205 children affected by HIV and AIDS between the age group of 12 to 17 were interviewed in selected two districts (Coimbatore and Salem) in Tamilnadu. Written consent from parents/guardians and assent from the child were obtained. A semi-structured interview schedule was used to collect the information on children caregiving responsibilities and its related issues. Pediatric Quality of Life Inventory™ (PedsQL™) tool were used to assess the quality of life. Both descriptive and association analysis including Analysis of variance (ANOVA) were carried out. Results: Mean age of the respondent children was 14.5 (sd 1.59) and 53.9% female children and 58.75 living in rural; Overall 59% of the children perform caregiving activities to the infected family members and siblings; 42% of the children perform both caregiving and household activities. More male children engaged in specific caregiving activities and more female children engaged in household activities (P<0.05). Quality of life of children (Physical health, Emotional health, peer relationships and school performance) who perform caregiving activities is lesser than those does not perform (P<0.05). Conclusions: Quality of life (QOL) of children living in HIV infected families are affected due to early caregiving and household activities. Need prioritization of policy and programmes towards.rn