Aim: To identify sleep-domains as well as clinical features in children with trisomy 21 that may shed light on a possible sleep disturbance as compared with typically developing (TD) age-matched-controls. Materials and methods: A convenient sample of 100 Saudi Arabian children between the ages of 3–12 were invited to participate from several schools and centers in Riyadh during February 2018 to April 2018. Fifty of these children had trisomy 21, and 50 were TD age-matched-controls. A clinical examination of participants’ oral characteristics as well as the Wisconsin's 22 item Children's Sleep Habit Questionnaire (CSHQ) were utilized to help identify the impact of these variables on sleep quality. Results: Sleep domains that harbored strong evidence in differences between the two groups were sleep anxiety, parasomnia, and sleep-disordered-breathing. The clinical features unique to trisomy 21 were Mallampati score, macroglossia, lip-incompetence, tongue-ridging, and wear-facets. Conclusion: Clinical features and sleep quality coexist, providing better insight into the degree of sleep disturbance a child with trisomy 21 may have. Clinical significance: Dental clinicians must consider such factors that preclude to poor sleep, which might place children with trisomy 21 at a further disadvantage despite the fact that their baseline is already at risk of being at such a stage.