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Our study aimed to evaluate the social deprivation score in families with a child with Prader-Willi syndrome (PWS) and analyze its impact on the occurrence of obesity in the affected child. We included 147 children with PWS followed in our reference center with Evaluation of the Deprivation and Inequalities of Health in Healthcare Centres by the EPICES score. Deprivation (EPICES ≥ 30) was found in 25.9% of the population. Compared with the non-obese children, children with obesity had more deprived families, 50.0 vs. 18.0% (p = 0.0001); were older, with a median of 10.1 vs. 6.0 years (p = 0.0006); were less frequently treated with growth hormone (GH), 80.6 vs. 91.9% (p = 0.07). The mothers of obese children were more frequently obese, 46.9 vs. 13.3% (p < 0.0001), and achieved high study levels less frequently (≥Bac+2), 40.9 vs. 70.1% (p = 0.012). The multivariate logistic regression indicated that age, living in a deprived family, and having a mother with overweight/obesity were significantly associated with an increased risk of obesity (respectively, OR = 3.31 (1.26–8.73) and OR = 6.76 (2.36–19.37)). The same risk factors of obesity observed in the general population were found in children with PWS. Families at risk, including social deprivation, will require early identification and a reinforced approach to prevent obesity. [ABSTRACT FROM AUTHOR]