In Caucasians and Native Americans living at altitude, hemoglobin mass is increased in spite of erythropoietin concentrations ([Epo]) not markedly differing from sea level values. We hypothesized that a nocturnal decrease of arterial oxygen saturation (SaO2) causes a temporary rise of [Epo] not detected by morning measurements. SaO2 (continuous, finger oximeter) and [Epo] (ELISA, every 4 h) were determined in young highlanders (altitude 2600 m) during 24 h of usual daily activity. In Series I (six male, nine female students), SaO2 fell during the night with the nadir occurring between 01:00 and 03:00; daily means (range 92.4–95.2%) were higher in females (+1.7%, P < 0.01). [Epo] showed opposite changes with zenith occurring at 04:00 without a sex difference. Mean daily values (22.9 ± 10.7SD U/L) were higher than values obtained at 08:00 (17.2 ± 9.5 U/L, P < 0.05). In Series II (seven females), only SaO2 was measured. During follicular and luteal phases, SaO2 variation was similar to Series I, but the rhythm was disturbed during menstruation. While daily [Epo] variations at sea level are not homogeneous, there is a diurnal variation at altitude following changes in SaO2. Larger hypoventilation-dependent decreases of alveolar PO2 decreases during the night probably cause a stronger reduction of SaO2 in highlanders compared to lowlanders. This variation might be enlarged by a diurnal fluctuation of Hb concentration. In spite of a lower [Hb], the higher SaO2 in women compared to men led to a similar arterial oxygen content, likely explaining the absence of differences in [Epo] between sexes.