Biomarker assessment is based on quantifying several proteins and metabolites. Recent developments in proteomics and metabolomics have enabled detection of these small molecules in biological samples and exploration of the underlying disease mechanisms in obstructive sleep apnea (OSA). This systemic review was performed to identify biomarkers, which were only detected by chromatography and/or mass spectrometry (MS) and to discuss the role of these biomarkers in the field of OSA.We systemically reviewed relevant articles from PubMed and EMBASE referring to proteins and metabolite profiles of biological samples in patients with OSA. The analytical platforms in this review were focused on chromatography and/or MS.In total, 30 studies evaluating biomarkers in patients with OSA using chromatography and/or MS methods were included. Numerous proteins and metabolites, including lipid profiles, adrenergic/dopaminergic biomarkers and derivatives, amino acids, oxidative stress biomarkers, and other micromolecules were identified in patients with OSA.Applying chromatography and/or MS methods to detect biomarkers helps develop an understanding of OSA mechanisms. More proteomic and metabolomic studies are warranted to develop potential diagnostic and clinical monitoring methods for OSA.