A cross-sectional study was conducted to determine the social factors and quality of life of HIV infected children attending the Pediatric Infectious Disease Clinic, Sappasithiprasong Hospital, Ubon Ratchathani Province, Thailand. Data were collected during October-November 2008, by interviewing caretakers and their children using a structured questionnaire. The children's families were in need of improved social support (84.5%), since community resources provided limited support, such as clothes, food, financial support, consultation, and information. The HIV infected children's quality of life needed improvement (78.7%). The factors associated with quality of life included having others as main caretakers (OR 4.64, 95% CI 1.45-14.78), parental death (OR 4.19, 95% CI 1.55-11.31), age of caregivers above 45 years old (OR 9.52, 95% CI 2.62-34.53), and family income less than THB 5,000 per month (OR 5.25, 95% CI 1.14-23.39). However, on multivariate analysis, only age of caregiver was a significant predictor for quality of life of the child. Children who were cared for by caregivers aged 45 years or above had a better quality of life than those whose caregivers were 20-45 years old (OR 6.32, 95% CI 1.12-35.62). Therefore, to improve quality of life among HIV infected children, age of caregiver is an important factor to be considered. Government and non-government organizations should focus on supporting caregivers in terms of food, financial, and emotional support based on resources available in the community.