BACKGROUND Sleep-disordered breathing may impair cerebral oxygenation in patients with OSA syndrome, in particular during altitude travel. We studied cerebral tissue oxygenation (CTO) at low and moderate altitude in patients with OSA and evaluated whether acetazolamide improved CTO. METHODS Eighteen patients with OSA living at < 600 m discontinued CPAP therapy during studies in Zurich (490 m) and during two sojourns of 3 days in the Swiss Alps (2 days at 1,860 m and 1 day at 2,590 m) separated by a 2-week washout period at < 600 m. Patients received acetazolamide (2 × 250 mg/d) or placebo at altitude in a randomized, double-blind, crossover design. Nocturnal polysomnography, including CTO monitoring by near-infrared spectroscopy (NIRS), was performed. RESULTS At 490 m, medians of CTO, peripheral oxygen saturation as measured by pulse oximetry (Spo2), and apnea/hypopnea index were 65%, 93%, and 57.3/h, respectively. At 2,590 m, on placebo, the corresponding values were 59%, 86%, and 86.4/h, respectively (P < .05, all corresponding comparisons). Acetazolamide increased CTO and Spo2 at 2,590 m by mean values of 2% (95% CI, 0%-4%) and 2% (95% CI, 1%-3%), respectively, and reduced the apnea/hypopnea index by 23.4/h (95% CI, 14.0-32.8/h) (P < .05, all changes). Cerebral total hemoglobin concentration, a NIRS-derived surrogate reflecting regional cerebral blood volume, increased by a similar degree in response to apneas at 490 m and 2,590 m and during acetazolamide and placebo treatment. CONCLUSIONS In patients with OSA staying at altitude, nocturnal cerebral and arterial oxygenation were reduced in association with exacerbated sleep apnea. Acetazolamide partially improved CTO, Spo2, and sleep apnea without impairing the cerebral blood flow response to apneas. BACKGROUND ClinicalTrials.gov; No.: NCT00714740; URL: www.clinicaltrials.gov.