The respiratory responses in the few previous studies evaluating the effects of short-term unopposed estrogen therapy on breathing in postmenopausal women have been inconsistent. We performed a study to investigate whether long-term estrogen therapy would prevent age-related decline in nocturnal arterial oxyhemoglobin saturation and whether higher serum estradiol concentration is associated with better arterial oxyhemoglobin saturation.Sixty-four healthy postmenopausal women were followed-up for 5 years in a 5-year prospective open follow-up study. The women were users or non-users of estrogen therapy according to their personal preference.Mean overnight arterial oxyhemoglobin saturation was similar at baseline (94.3±1.1%) and after follow-up (94.5±1.6%). Present estrogen users had higher mean arterial oxyhemoglobin saturation (95.2±1.4%) than present non-users (94.0±1.5%), when adjusted for age and body mass index (p=0.042). The change in mean arterial oxyhemoglobin saturation during follow-up was not associated with serum estradiol concentration at baseline but associated with estradiol at follow-up (p=0.042), when adjusted for age and body mass index. At follow-up, women with higher serum estradiol concentration had also higher mean nocturnal arterial oxyhemoglobin saturation (Pearson r=0.29, p=0.019) and lower apnea-hypopnea index (Spearman r=−0.28, p=0.031). The pooled current estrogen users spent proportionally less time with SaO 2 below 90% than non-users (ANCOVA adjusted for age and BMI, p=0.017).Estrogen use and especially high serum estradiol concentration predict higher mean overnight arterial oxyhemoglobin saturation. The present data suggest that estrogen therapy has favorable respiratory effects.