OBJECTIVES To determine whether psychosocial well-being is associated with the health-related quality of life (HRQOL) of people with Usher syndrome. SETTING The survey was advertised online and through deafblind-related charities, support groups and social groups throughout the UK. PARTICIPANTS 90 people with Usher syndrome took part in the survey. Inclusion criteria are having a diagnosis of Usher syndrome, being 18 or older and being a UK resident. PRIMARY AND SECONDARY OUTCOME MEASURES All participants took part in a survey that measured depressive symptoms, loneliness and social support (predictors) and their physical and mental HRQOL (outcomes). Measured confounders included age-related, sex-related and health-related characteristics. Hierarchical multiple linear regression analyses examined the association of each psychosocial well-being predictor with the physical and mental HRQOL outcomes while controlling for confounders in a stepwise manner. RESULTS After adjusting for all confounders, psychosocial well-being was shown to predict physical and mental HRQOL in our population with Usher syndrome. Increasing depressive symptoms were predictive of poorer physical (β=-0.36, p<0.01) and mental (β=-0.60, p<0.001) HRQOL. Higher levels of loneliness predicted poorer mental HRQOL (β=-0.20, p<0.05). Finally, increasing levels of social support predicted better mental HRQOL (β=0.19, p<0.05). CONCLUSIONS Depression, loneliness and social support all represent important issues that are linked with HRQOL in a UK population with Usher syndrome. Our results add to the growing body of evidence that psychosocial well-being is an important factor to consider in people with Usher syndrome alongside functional and physical impairment within research and clinical practice.