Background <p>Sleep-related hypoventilation, particularly during rapid eye movement (REM) sleep, has been linked to pulmonary hypertension and recurrent exacerbations in individuals with advanced chronic respiratory or neuromuscular diseases. Overnight pulse oximetry (OPO) serves as a valuable screening tool to depict episodic oxygen desaturation resulting from sleep-related hypoventilation. However, differentiating nocturnal desaturation caused by physical activity from that attributable to sleep-related hypoventilation remains clinically challenging. This study aimed to determine whether the integration of accelerometer data with OPO readings can assist in distinguishing exertional nocturnal desaturation from desaturation due to sleep-related hypoventilation.</p> Methods <p>Between July 2021 and December 2022, a prospective enrollment was conducted among consecutive individuals with stable chronic respiratory disorders who reported worsening exertional dyspnea. Participants underwent overnight monitoring involving transcutaneous carbon dioxide pressure (PtcCO₂) and pulse oximetry integrated with accelerometer sensors. The number of exertion-associated desaturation events was compared between participant self-reports and acceleration-derived data. Additionally, the diagnostic accuracy of accelerometer-integrated pulse oximetry for detecting episodic nocturnal hypercapnia was assessed using PtcCO₂ monitoring as the reference standard. The primary endpoint was the patient-level diagnostic accuracy of accelerometer-integrated pulse oximetry in detecting episodic nocturnal hypercapnia.</p> Results <p>Thirty-six individuals were enrolled, with a median age of 78.0 (IQR: 72.0–82.0) years and a mean daytime arterial carbon dioxide pressure (PaCO₂) of 42.4 ± 6.9 mmHg. Of the 89 desaturation events observed, 56 (62.9%) were identified as exertion-related using accelerometer data, including 19 events (21.3%) that were not self-reported. The device demonstrated a sensitivity of 100% (95% CI: 79.6–100%) and a specificity of 75.7% (95% CI: 64.8–84.0%) in identifying episodic nocturnal hypoxia associated with hypercapnia. At the patient level, sensitivity and specificity were 100% (95% CI: 100–100%) and 73.1% (95% CI: 53.9–86.3%), respectively. At the event level, sensitivity and specificity were 100% (95% CI: 79.6–100%) and 75.7% (95% CI: 64.8–84.2%), respectively.</p> Conclusion <p>Among individuals with suspected sleep-related breathing disorders, accelerometer-integrated pulse oximetry may serve as a valuable tool to distinguish nocturnal desaturation episodes caused by exertion from those due to sleep-related hypoventilation. These findings suggest that accelerometer-integrated pulse oximetry could offer a feasible screening method for detecting sleep-related hypoventilation in outpatient settings lacking access to PtcCO₂ monitoring.</p>