This study evaluated the effects of 2-4 months of continuous positive airway pressure (CPAP) treatment on previously demonstrated P300 latency prolongations in obstructive sleep apnea (OSA). Subjects with severe OSA (respiratory disturbance index > 40/hour sleep) were administered polysomnograms, auditory and visual P300 testing using 31 scalp electrodes, and multiple sleep latency testing before and after treatment with CPAP for 2-4 months. Despite significant improvements in sleep and respiratory variables and the mean sleep latency, there were no significant P300 changes. Obstructive sleep apnea patients had prolonged visual P300 latency compared to normals, both before and after treatment. Prolongations in P300 latency that are resistant to the acute effects of CPAP may suggest that OSA causes physiological cortical changes that are unrelated to sleepiness and may be resistant to treatment.