Chronic illness during childhood can also cause changes in the health-related quality of life (HrQoL) of the individual’s family members.This study aimed to evaluate the HrQoL among healthy siblings of children with chronic illness.Cross-sectional study.We enrolled healthy siblings of 191 children with a chronic illness (cerebral palsy, epilepsy, diabetes, celiac disease, hematological oncologic disease, or asthma) and those siblings of 100 healthy children for quality of life evaluation. We administered the Pediatric Quality of Life Inventory questionnaire; the physical health and psychosocial health score were calculated using individual sibling and parent responses. The primary endpoint was the comparison of HrQoL scores of healthy siblings of 191 children with a chronic illness and those siblings of 100 healthy children.The physical health, psychosocial health, and total health scores of healthy siblings of children with a chronic illness were significantly lower than those of siblings of healthy children (p<0.001). In the chronic disease group, the lowest psychosocial health score was found in the cerebral palsy, hematologic/oncologic disease and asthma groups (p<.001). The global impact on the quality of life for healthy siblings of children with a chronic disease was significantly higher in children’s self-reports than in parents’ reports (30.4% vs. 15.1%, p<0.05).This study showed that most of the healthy siblings of children with a chronic illness are physically and psychosocially affected. In healthy siblings, we observed a global impact on the HrQoL, including psychosocial scores, and a low level of parental awareness about this situation. This might increase the risk of emotional neglect and abuse in these children. Thus, special support programs are needed for the families of children with chronic illness.