Background: It is well known that oxygen saturation as measured by pulse oximetry (SpO2) decreases as altitude increases. However, how SpO2 changes across childhood, and more specifically during sleep/wake states, at different high altitudes are less well understood. We aimed to perform a systematic review of all studies with direct SpO2 measurement in healthy children living at high altitude (>2500 meters above sea level) to address these questions. Methods: MEDLINE, EMBASE, and SciELO databases were searched up to December 2018. Two independent reviewers screened the literature and extracted relevant data. Results: Of 194 references, 20 studies met the eligibility criteria. Meta-analysis was not possible due to the use of different oximeters and/or protocols for data acquisition and reporting of different SpO2 central tendency and dispersion measures. The most relevant findings from the data were: (1) SpO2 is lower as altitude increases; (2) at high altitude, SpO2 improves with age through childhood; (3) SpO2 is lower during sleep and feeding in comparison to when awake, this SpO2 gap between wake and sleep states is more evident in the first months of life and narrows later in life; (4) SpO2 dispersion (interindividual variation) is higher at younger ages, and more so during sleep; (5) In 6/20 studies, the SpO2 values were nonnormally distributed with a consistent left skew. Conclusions: At high altitude, the mean/median SpO2 increases in children with aging; a significant gap between wake and sleep states is seen in the first months of life, which narrows as the infant gets older; SpO2 dispersion at high altitude is wider at younger ages; at high altitude, SpO2 shows a nonnormal distribution skewed to the left; this bias becomes more evident as altitude increases, at younger ages and during sleep.