Background: The increased life expectancy of people with Down syndrome puts pressure on parents, who are usually the main caregivers but who find caring more difficult as they get older. The quality of the support provided by brothers and sisters depends on the intra-family relationships they build when growing up. Methods: 121 adult siblings of people with Down syndrome completed a questionnaire on their perceptions of their childhood relationships. Results: Brothers' and sisters' relationships with a sibling with Down syndrome were mostly (very) positive, but this was not always the case for their relationships with their parents and other siblings. Factors affecting these relationships include respondent's sex, number of siblings, and sibling position. Conclusions: In addition to simple risk and protective factors, we identified parameters that should be taken into account when providing support to siblings and parents of people with Down syndrome.