To assess the quality of life (QOL) and the psychosocial problems of HIV infected children. The present study was a comparative, cross-sectional survey conducted in the clinic of a tertiary care hospital in north India from July-December 2007. Children suffering from cystic fibrosis (CF) were chosen as a comparison group. Children (3) 6 yr of age with HIV infection or Cystic Fibrosis, with no acute illness at the time of survey were included in the study. Quality of life of the enrolled children was assessed by using the Pediatric Quality of Life Inventory (PedsQL). Pediatric Symptom Checklist (PSC) was used for assessing the psychosocial problems in the enrolled children. Forty one HIV infected and 30 children with cystic fibrosis were enrolled. According to child self -report in the PedsQL 4.0, the difference of perceived physical health status between the two study groups was statistically significant (p=0.04), with HIV infected children demonstrating a better QOL in this domain. A significantly greater number of children with cystic fibrosis (8/30 or 26.67%) suffered from psychosocial problems as compared to HIV children (3/41 or 7.32%) [p=0.026]. The quality of life and psychosocial functioning is reasonably good in children with HIV infection. Thus, we should strive to maintain and optimize the overall quality of life of these children so that they can have a productive and meaningful future.