AbstractThe physiological sequelae of pre‐term birth might influence the responses of this population to hypoxia. Moreover, identifying variables associated with development of acute mountain sickness (AMS) remains a key practically significant area of altitude research. We investigated the effects of pre‐term birth on nocturnal oxygen saturation () dynamics and assessed the predictive potential of nocturnal ‐related metrics for morning AMS in 12 healthy adults with gestational age < 32 weeks (pre‐term) and 12 term‐born control participants. Participants spent one night at a simulated altitude of ∼4200 m (normobaric hypoxia; fraction of inspired O2 = 0.141), with nocturnal and heart rate recorded continuously at the fingertip using pulse oximetry and with morning AMS assessed using the Lake Louise scale. Pre‐term and term‐born participants had similar nocturnal mean (mean ± SD; 77% ± 3% vs. 77% ± 4%; P = 0.661), minimum (median[IQR]; 67[4]% vs. 69[5]%; P = 0.223), relative time spent with  < 80% (72% ± 29% vs. 70% ± 27%; P = 0.879) and mean heart rate (79 ± 12 vs. 71 ± 7 beats/min; P = 0.053). However, the increase in between the two halves of the night was blunted with prematurity (−0.12% ± 1.51% vs. 1.11% ± 0.78%; P = 0.021). Moreover, the cumulative relative desaturation‐based hypoxic ‘load’ was higher with prematurity (32[26]%min/h vs. 7[25]%min/h; P = 0.039), underpinned by increased desaturation frequency (69[49] vs. 21[35] counts/h; P = 0.009). Mean , minimum , morning and relative time spent with  < 80% predicted AMS incidence better than a random classifier exclusively in the pre‐term group, with no other variables predictive of AMS in the two groups separately or combined. Overall, pre‐term birth might alter nocturnal dynamics and influence AMS prediction in severe hypoxia.