Measuring peripheral oxygen saturation (SpO2) with pulse oximeters at the point of care is widely established. However, since SpO2 is dependent on ambient atmospheric pressure, the distribution of SpO2 values in populations living above 2000 m a.s.l. is largely unknown. Here, we propose and evaluate a computer model to predict SpO2 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 SpO2 model that takes physiological adaptation of permanent residents into account. From this model, we derived an altitude-adaptive abnormal SpO2 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 SpO2 range below 2,000 m a.s.l. but the medians never differed more than 2.3% across all altitudes. Our threshold estimated abnormal SpO2 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 SpO2, it could assist practitioners in interpreting SpO2 values for diagnosis, prognosis, and oxygen administration at higher altitudes.NEW & NOTEWORTHY Our model describes the altitude-dependent decrease of SpO2 in healthy pediatric residents based on physiological equations and can be adapted based on measureable clinical parameters. The proposed altitude-specific abnormal SpO2 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.