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Measuring peripheral oxygen saturation ([Formula: see text]) with pulse oximeters at the point of care is widely established. However, since [Formula: see text] is dependent on ambient atmospheric pressure, the distribution of [Formula: see text] values in populations living above 2000 m a.s.l. is largely unknown. Here, we propose and evaluate a computer model to predict [Formula: see text] values for pediatric permanent residents living between 0 and 4,000 m a.s.l. Based on a sensitivity analysis of oxygen transport parameters, we created an altitude-adaptive [Formula: see text] model that takes physiological adaptation of permanent residents into account. From this model, we derived an altitude-adaptive abnormal [Formula: see text] threshold using patient parameters from literature. We compared the obtained model and threshold against a previously proposed threshold derived statistically from data and two empirical data sets independently recorded from Peruvian children living at altitudes up to 4,100 m a.s.l. Our model followed the trends of empirical data, with the empirical data having a narrower healthy [Formula: see text] range below 2,000 m a.s.l. but the medians never differed more than 2.3% across all altitudes. Our threshold estimated abnormal [Formula: see text] in only 17 out of 5,981 (0.3%) healthy recordings, whereas the statistical threshold returned 95 (1.6%) recordings outside the healthy range. The strength of our parametrized model is that it is rooted in physiology-derived equations and enables customization. Furthermore, as it provides a reference [Formula: see text], it could assist practitioners in interpreting [Formula: see text] values for diagnosis, prognosis, and oxygen administration at higher altitudes.    NEW &amp; NOTEWORTHY Our model describes the altitude-dependent decrease of [Formula: see text] in healthy pediatric residents based on physiological equations and can be adapted based on measureable clinical parameters. The proposed altitude-specific abnormal [Formula: see text] threshold might be more appropriate than rigid guidelines for administering oxygen that currently are only available for patients at sea level. We see this as a starting point to discuss and adapt oxygen administration guidelines.

Physiologically driven, altitude-adaptive model for the interpretation of pediatric oxygen saturation at altitudes above 2,000 m a.s.l.