People living with MND (PlwMND) are at risk of altitude-related hypoxia during flight. The Hypoxic Challenge Test (HCT) determines whether in-flight oxygen is required but can be expensive and inaccessible. To assist with travel recommendations, we investigated the relationship between altitude simulation-induced hypoxemia and baseline lung function. Retrospective audit of clinical database of PlwMND who had HCT and lung function. Pearson's correlation assessed relationships between oxygen saturation at altitude (AltSpO2) and lung function. Univariate logistic regression analysis and receiver operator characteristic (ROC) curves determined associations between lung function and HCT pass or fail. Between 2004-2023, 50 PlwMND were identified (median (IQR) diagnosis to HCT = 11.6 (16.9) months, mean ± SD forced vital capacity (FVC) = 2.4 ± 0.9 liters). Ten patients dropped below 85% SpO2 during testing (HCT fail). Baseline SpO2 was associated with AltSpO2 (r = 0.64) and predicted HCT pass or fail (OR 2.0 [95% CI 1.2-3.4], area under ROC curve (AUC) =0.8 [0.6-1.0]), as did FVC (AUC = 0.8 [0.6-0.9]). PlwMND with a FVC > 2.7L or a resting SpO2 > 97% are likely to pass HCT, whereas all those with FVC < 1L and SpO2 < 92% failed. PlwMND with FVC >2.7L or SpO2 >97% are unlikely to require oxygen or ventilatory supports for airline travel. A FVC below 2.7L will require a HCT to confidently determine HCT outcome, with testing still required for FVC <1L or baseline SpO2 <92%, to provide evidence to the airlines for in-flight respiratory support.