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BACKGROUND Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repetitive upper airway obstruction during sleep, thereby resulting in oxygen desaturation, frequent arousals, and increased sympathetic activity. Wearable devices that measure peripheral oxygen saturation have been developed for the screening of OSA. OBJECTIVE This study aimed to validate and characterize the estimation function of oxygen saturation measured by wrist-worn reflectance pulse oximetry during sleep and to predict the derived OSA using the oxygen desaturation index (ODI). METHODS Oxygen saturation was simultaneously measured using reflectance pulse oximetry from the Samsung Galaxy Watch 4 series (SM-R890N, SM-R860N, Samsung Electronics Co.; GW4) and transmittance pulse oximetry from polysomnography as a reference (SpO2Ref). The performance was evaluated by the root mean squared error (RMSE) and coverage rate, and it was compared according to the apnea-hypopnea index (AHI). The GW4-ODI was used to predict moderate to severe OSA. RESULTS A total of 97 adults (44.4 ± 13.0 years; men 76.3%, women 23.7%) participated in this study. Depending on the AHI, participants were classified as either normal (n=18), mild (n=21), moderate (n=23), or severe OSA (n=35). Wrist-worn reflectance pulse oximetry showed an overall RMSE of 2.3% and negligible bias of -0.2%. A Bland-Altman density plot showed good agreement of oxygen saturation between GW4 and the reference pulse oximeter. RMSEs were 1.65 ± 0.57%, 1.76 ± 0.65%, 1.93 ± 0.54%, and 2.93 ± 1.71% for normal, mild, moderate, and severe OSA, respectively. GW4-ODI ≥5/h had the highest predictive ability for moderate to severe OSA with a sensitivity of 89.7%, a specificity of 64.1%, an accuracy of 79.4%, and an area under the curve of 0.908 (95% CI, 0.852–0.963). CONCLUSIONS GW4 was successfully validated for measuring oxygen saturation with reflectance pulse oximetry during sleep. This study demonstrates the feasibility of GW4 for screening moderate to severe OSA.