Obstructive sleep apnea (OSA) is a common sleep disorder, and continuous positive airway pressure (CPAP) is the most effective treatment. Poor adherence is one of the major challenges in CPAP therapy. The recent boom of wearable optical sensors measuring oxygen saturation makes at-home multiple-night CPAP titrations possible, which may essentially improve the adherence of CPAP therapy by optimizing its pressure in a real-life setting economically. We tested whether the oxygen desaturations (ODs) measured in the arm muscle (arm_OD) by gold-standard frequency-domain multi-distance near-infrared spectroscopy (FDMD-NIRS) change quantitatively with titrated CPAP pressures in OSA patients together with polysomnography. We found that the arm_OD (2.08 ± 1.23%, mean ± standard deviation) was significantly smaller (p-value textless 0.0001) than the fingertip OD (finger_OD) (4.46 ± 2.37%) measured by a polysomnography pulse oximeter. Linear mixed-effects models suggested that CPAP pressure was a significant predictor for finger_OD but not for arm_OD. Since FDMD-NIRS measures a mixture of arterial and venous OD, whereas a fingertip pulse oximeter measures arterial OD, our results of no association between arm_OD and finger_OD indicate that the arm_OD mainly represented venous desaturation. Arm_OD measured by optical sensors used for wearables may not be a suitable indicator of the CPAP titration effectiveness.