Obstructive sleep apnea is characterized with chronic intermittent hypoxia and sleep fragmentations. The sequels of OSA included excessive daytime sleepiness, cardiovascular disease, and neurocognitive dysfunction which could be reversed with continuous positive airway pressure (CPAP). A couple of biologic pathways have been associated with the phenotyping of OSA which included craniofacial morphology, ventilator control, body fat distribution/metabolism, and sleepiness vulnerability. Metabolomics, a recently developed technique to detect metabolomic profiles, could help to understand the disease pathophysiology and explore biomarkers. So far, only one paper studied the metabolomic profile in patients with OSA where putative identifications of 14 statistically significant features were profiled. Our pilot study comparing the metabolic profiling in OSA patients randomly assigned to therapeutic and subtherapeutic CPAP showed CPAP treatment did alter the metabolomic profile. Seventeen metabolites in three biologic pathways and 13 metabolites in the six biologic pathways were identified in therapeutic and subtherapeutic CPAP, respectively. Sixteen metabolites in three biologic pathways were identified by comparing two groups. However, there were a couple of weakness in studies in the literature and ours. Furthermore, the direct causal relationship of the profiled metabolites and OSA needs to be clarified. Therefore, we plan to compare the metabolic profiling in control subjects and healthy OSA patients, before and after six-month CPAP treatment, to identify candidate metabolites involved in biologic pathways attributing to phenotyping and response to CPAP treatment. Furthermore, candidate metabolites involved in biologic pathways, especially pathways of ROS, inflammation, and metabolism, will be validated in the intermittent hypoxia model of peripheral monocytes.