Early parent-child interactions (PCI) impact social cognitive development. Relatedly, children with various developmental disorders exhibit abnormal parental attachment relationships. Parental characteristics and behaviors can impact PCI and socioemotional development as well. No research has examined the parent-child dynamic in Prader-Willi syndrome (PWS), a neurodevelopmental disorder that presents with social cognitive deficits. This article provides a preliminary characterization of PCI quality and parenting stress in 17 PWS parent-child dyads, children ages 3–5 years, in comparison to 20 typically developing children and their parent. Results suggest early PCI disruption in preschoolers with PWS and their parents report increased levels of stress in various domains. These findings have important implications not only on parent well-being in PWS but its impact on child development.