BACKGROUND: Prader-Willi syndrome (PWS), is a genetically determined neurodevelopmental disorder, associated with intellectual disabilities and a high incidence of obesity, diabetes mellitus, and respiratory disorders. We hypothesised that COVID-19, a viral infection which more severely affects people with these conditions, would, in people with PWS, present atypically and result in severe outcomes. METHOD: A structured on-line questionnaire was piloted with parents and professionals at the International Prader-Willi Syndrome Organization (IPWSO) and promoted internationally through their global network. Family members/other carers were asked to complete if someone they cared for with PWS was strongly suspected or confirmed as having COVID-19. RESULTS: Over 1 year of the pandemic 72 responses were received, 47 adults, 25 children. The following underlying conditions were present: 16 people with PWS were overweight and 18 obese, five had diabetes mellitus and 18 sleep apnoea. Main presenting symptoms were raised temperature, fatigue/daytime sleepiness, dry cough, headache/pain, and feeling unwell, with illnesses generally lasting less than a week. Length of illness was not significantly related to age, BMI, sex, or genetic subtype. No one was ventilated or in an intensive care unit or died, one person was in hospital for four days needing oxygen. CONCLUSIONS: Contrary to our hypothesis, the PWS cohort had asymptomatic infection or mild illness. A possible explanation, supported by anecdotal evidence from parents and professional carers, is that people with PWS have a degree of innate immunity to viral infections. However, likely selection effects and a relatively low number of responses means that further evidence is needed to test this hypothesis.