Obstructive sleep apnea (OSA), the commonest form of sleep-disordered breathing, is characterized by recurrent episodes of intermittent hypoxia and sleep fragmentation. This study evaluated microarray measures of gene transcript levels in OSA subjects compared to age and BMI matched healthy controls. Measurements were obtained before and after: (a) a night of normal sleep in controls; and (b) a night of untreated apnea in OSA patients. All subjects underwent full polysomnography. mRNA from the whole blood samples was analyzed by HG-U133A and B Affymetrix GeneChip arrays using Spotfire 7.2 data analysis platform. After sleep in OSA patients, changes were noted in several genes involved in modulation of reactive oxygen species (ROS), including heme oxygenase 1, superoxide dismutase 1 and 2, and catalase. Changes were also observed in genes involved in cell growth, proliferation, and the cell cycle such as cell division cycle 25B, signaling lymphocyte activating molecule (SLAM), calgizzarin S100A11, B-cell translocation gene, Src-like adapter protein (SLAP), and eukaryotic translation initiation factor 4E binding protein 2. These overnight changes in OSA patients are suggestive of activation of several mechanisms to modulate, and adapt to, increased ROS developing in response to the frequent episodes of intermittent hypoxia.