Health-Related Quality of Life (HRQOL) and anxiety were measured in 233 school-age siblings of individuals with Autism Spectrum Disorders (ASD) and siblings of Typically Developing (TD) children in Greece. The aim of the study was to investigate for any association between siblings' HRQOL or anxiety and parental mental health, perceived social support as well as major demographic factors. It was found that the disability group (ASD-sibs) showed elevated anxiety levels and poorer HRQOL than controls. In hierarchical multiple regression models, the anxiety of ASD-sibs was significantly associated with parental anxiety independent of parental perceived social support and demographic factors, whereas the HRQOL of ASD-sibs was associated with perceived social support independent of parental physical and mental health and demographic factors.