Obstructive sleep apnea (OSA) is a major public health problem affecting approximately 2% to 3% of children. However, snoring, the cardinal symptom of OSA, affects at least 5-fold more children, such that evaluation by overnight polysomnography (ONP) is required for the diagnosis. ONP is laborious, expensive, and relatively unavailable to children. Proteomic mass spectrometry coupled with bioinformatic tools provide valuable means for discovery of new biomarkers in serum for a variety of human disorders. The possibility exists that snoring children with and without OSA may exhibit different protein expression profiles in serum that could be useful in the development of novel diagnostic tools for this condition. The proteomic patterns of 20 children with OSA and of 20 children with habitual primary snoring but no evidence of OSA (HS) were evaluated using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Linear discriminative analysis identified three differentially regulated proteins with molecular masses of 5896, 3306, 6068 Da that were capable of diagnosing OSA with 93% sensitivity and 90% specificity. Thus, the proteomic signatures of sera from children with OSA differ from those of HS who do not fulfill the current criteria for treatment. Identification and sequencing of those differentially expressed proteins discovered through proteomic strategies may lead to future development of serum-based diagnostic tests for OSA in snoring children.