Central sleep apnea (CSA) is characterized by periodic breathing (PB) during sleep, defined as intermittent periods of apnea/hypopnea and hyperventilation, with associated acute fluctuations in oxyhemoglobin saturation (SO2). CSA has an incidence of ∼50% in heart failure patients but is universal at high altitude (HA; ≥2,500 m), increasing in severity with further ascent and/or time at altitude. However, whether PB is adaptive, maladaptive, or neutral with respect to sleeping SO2 at altitude is unclear. We hypothesized that PB severity would improve mean sleeping SO2 during acclimatization to HA due to relative, intermittent hyperventilation subsequent to each apnea. We utilized portable sleep monitors to assess the incidence and severity of CSA via apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), and peripheral oxygen saturation ([Formula: see text]) during sleep during two ascent profiles to HA in native lowlanders: 1) rapid ascent to and residence at 3,800 m for 9 days/nights (n = 21) and 2) incremental ascent to 5,160 m over 10 days/nights (n = 21). In both ascent models, severity of AHI and ODI increased and mean sleeping [Formula: see text] decreased, as expected. However, during sleep on the last night/highest altitude of both ascent profiles, neither AHI nor ODI were correlated with mean sleeping [Formula: see text]. In addition, mean sleeping [Formula: see text] was not significantly different between high and low CSA. These data suggest that CSA is neither adaptive nor maladaptive with regard to mean oxygen saturation during sleep, owing to the relative hyperventilation between apneas, likely correcting transient apnea-mediated oxygen desaturation and maintaining mean oxygenation.NEW & NOTEWORTHY Central sleep apnea (CSA) is universal during ascent to high altitude, with intermittent and transient fluctuations in oxygen saturation, but the consequences on mean sleeping blood oxygenation are unclear. We assessed indices of CSA and mean sleeping peripheral oxygen saturation ([Formula: see text]) during ascent to high altitude using two ascent profiles: rapid ascent and residence at 3,800 m and incremental ascent to 5,160 m. The severity of CSA was not correlated with mean sleeping [Formula: see text] with ascent.