Study Objectives: This study aimed to examine the acute effects of high altitude (HA) on sleep disordered breathing (sleep apnea and nocturnal hypoxemia) and acute mountain sickness and to characterize acclimatization over time. Methods: Ten native lowlanders residing at sea level (SL) completed the Lake Louise Score (LLS) and underwent nocturnal polygraphy (ApneaLink Plus) for nine consecutive nights (N1-N9) at HA (2,761 m) and two nights before and after HA. Nocturnal oxygen profiles were assessed by measuring the mean nocturnal oxyhemoglobin saturation (S(p)O(2)) during sleep, and sleep apnea severity as assessed by measuring the Apnea-Hypopnea Index (AHI). Mixed-effects linear regression was used to model responses in outcomes (mean nocturnal S(p)O(2), logAHI, and LLS) between HA and SL. Changes in S(p)O(2) and AHI were examined in subgroups with mild versus marked nocturnal S(p)O(2) and low versus high AHI during exposure to HA and compared between subgroups. Results: Compared with SL, the mean nocturnal S(p)O(2) was lower (p < 0.0001) and AHI was higher (p < 0.0001) at HA. The mean nocturnal S(p)O(2) increased progressively (p < 0.001), whereas AHI remained high (p < 0.978) and relatively unchanged over nine successive nights at HA. Those with markedly reduced S(p)O(2) upon arrival at HA exhibited progressive increases in the mean nocturnal S(p)O(2) over time at HA compared with those with mild nocturnal desaturation. LLS rose at HA, but no differences were observed between subgroups. Conclusions: In healthy HA sojourners, the mean nocturnal S(p)O(2) increased progressively over time, whereas AHI remained elevated, suggesting distinctive phenotypes and acclimatization responses to HA.