We present the case of a 78-year-old female who experienced acute mental deterioration after vomiting. She showed severe hypercapnia without definite lung disease and hypoxic injury on brain image. After the acute period, she still had excessive daytime sleepiness, and the hypercapnia aggravated during the night. Polysomnography revealed severe obstructive sleep apnea, a sleep-related breathing disorder with a high apneahypopnea index of 60.2/h (mainly a hypopnea index of 59.0/h). She was diagnosed with combined obesity hypoventilation syndrome (OHS) and sleep-related breathing disorder, as the cause of daytime hypercapnia and excessive daytime sleepiness. Three months of successful bi-level positive airway pressure (BiPAP) therapy dramatically improved her daytime sleepiness and cognition. This case suggests that patients with OHS can be susceptible to hypoxic brain damage, and emphasizes the importance of the recognition and diagnosis of OHS and appropriate treatment with BiPAP therapy.