Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most common connective tissue disorder. However, few studies exist on psychiatric and sleep disorders in pediatric patients with hEDS. This study aims to describe psychiatric and sleep disorders and evaluate their impact on health-related quality of life (HRQoL) in pediatric patients with hEDS. As part of a longitudinal study, a convenience sample of 123 pediatric patients with hEDS, were recruited at a hEDS multidisciplinary clinic in sequential order over a seven-month period. Patient-reported outcomes were completed (Patient Reported Outcomes Measurement Information System Pediatric Profile Version 2 [PROMIS], Generalized Anxiety Disorder-7 [GAD-7], Adolescent Sleep Wake Scale [ASWS], and Pediatric Quality of Life Inventory Rheumatology Module [PEDS-QL Rheum]). The mean age was 15.8 years (SD = 2.7), the majority were female (92%) and Caucasian (92%). Most (86%) had at least one psychiatric diagnosis, with anxiety (80%) the most common, followed by depression (42%). Many (42%) also reported poor sleep. Correlations were seen between the GAD-7, PROMIS pain and HRQoL. Worse anxiety and depression were correlated with more sleep problems. Depression, GAD-7, and ASWS were also correlated with worse HRQoL. Performing regression analyses found anxiety and pain to be most predictive of HRQoL. Psychiatric and sleep disorders are prevalent in pediatric patients with hEDS and impact HRQoL negatively. Clinical focus on the anxiety and pain are important due to their impact on HRQoL.