Background: Sleep studies are laborious, expensive, inaccessible, and inconvenient for diagnosing OSA in children. Proteomic analyses may uncover specific protein clusters that are differentially expressed in urine of children with OSA. Subjects and Methods: Morning urine proteins from 60 children with polysomnographically-confirmed OSA and matched children with either primary snoring (PS; n=30) or controls (CO; n=30) were assessed with 2D-DIGE and mass spectroscopy. A total of 16 proteins that are differentially expressed in OSA were identified, and 7 were confirmed by either immunoblots or ELISA. Among the latter, receiver-operator curve analyses of urinary concentrations of uromodulin, urocortin 3, orosomucoid 1, and kallikrein assigned favorable predictive properties to these proteins. Furthermore, combinatorial approaches indicated that the presence of values beyond the calculated cut-off concentrations for 3 of the proteins yielded a sensitivity of 95% and a specificity of 100%. Conclusions: Proteomic approaches reveal that pediatric OSA is associated with specific and consistent alterations in urinary concentrations of specific protein clusters. Future studies aiming to validate this approach as a screening method of habitually snoring children appears warranted.