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Background Down syndrome is associated with poor sleep but little is known about its neural correlates. Aims The current research compared brain morphometry in youth with Down syndrome with parent-reported sleep problems (DS-S) to peers with Down syndrome (DS) and typical development (TD) without parent-reported sleep problems matched on age (M = 15.15) and sex ratio (62 % female). Methods and procedures Magnetic resonance imaging was completed on a 3 T scanner. Participants were stratified into groups based on parent-report: DS-S (n = 17), DS (n = 9), TD (n = 22). Brain morphometry, processed with the FreeSurfer Image Analysis Suite, was compared across groups. In addition, the co-occurrence of medical conditions in the DS groups was examined. Outcomes and results Youth with DS-S had reduced total, frontal, parietal, and temporal brain volumes relative to DS and TD peers. They also had higher rates of congenital heart defects than the DS-only group; however, this comorbidity did not appear to account for morphometry differences. Conclusions and implications Parent-reported sleep problems in DS appear to relate to global and localized volume reductions. These preliminary results have implications for understanding the neural correlates of poor sleep in DS; they also highlight the importance of examining relations between sleep and other medical comorbidities.