BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder associated with generalized autonomic dysfunction. Children with PWS are at increased risk of obstructive sleep apnea (OSA) and central sleep apnea (CSA), which are also associated with autonomic dysfunction and increased risk for cardiovascular disease later in life. This study aimed to investigate the autonomic control of heart rate (HR) in children with PWS. METHODS: 49 growth hormone naïve children with PWS (aged 2 months to 15 y) were individually matched for age, sex, obstructive apnea hypopnea index (OAHI), central apnea hypopnea index (CAHI) and BMI (children >2 y) with typically developing (TD) children. Multilevel modelling determined the effect of PWS on HR changes during obstructive and central respiratory events during sleep, between a 10s pre-event window, to the latter half of each respiratory event (late-event), and 15s post-event, accounting for respiratory disturbance index (OAHI + CAHI), age, arousal and event length. RESULTS: During sleep, children with PWS had a smaller percentage change in HR during obstructive events, from the pre-event to post-event (PWS: median 8.7% (IQR 3.6%,16.8%) TD: 15.6% (8.5%,25.7%, p < 0.01) and from late-event to post-event (PWS: 12.1% (6.4%,21.8%) TD: 16.8% (9.8%,29.5%), p < 0.05) phases. There was no difference between groups for central events. CONCLUSION: Our results demonstrate dampened autonomic control of HR in children with PWS. Further research is necessary to determine the implications of autonomic dysfunction in affected children on future overall health outcomes including their cardiovascular and neurocognitive health.