Abstract Study Objectives To evaluate wearable devices and machine learning for detecting sleep apnea in patients with stroke at an acute inpatient rehabilitation facility (IRF). Methods A total of 76 individuals with stroke wore a standard home sleep apnea test (ApneaLink Air), a multimodal, wireless wearable sensor system (ANNE), and a research-grade actigraphy device (ActiWatch) for at least 1 night during their first week after IRF admission as part of a larger clinical trial. Logistic regression algorithms were trained to detect sleep apnea using biometric features obtained from the ANNE sensors and ground truth apnea rating from the ApneaLink Air. Multiple algorithms were evaluated using different sensor combinations and different apnea detection criteria based on the apnea–hypopnea index (AHI ≥ 5, AHI ≥ 15). Results Seventy-one (96%) participants wore the ANNE sensors for multiple nights. In contrast, only 48 participants (63%) could be successfully assessed for obstructive sleep apnea by ApneaLink; 28 (37%) refused testing. The best-performing model utilized photoplethysmography (PPG) and finger-temperature features to detect moderate-severe sleep apnea (AHI ≥ 15), with 88% sensitivity and a positive likelihood ratio (LR+) of 44.00. This model was tested on additional nights of ANNE data achieving 71% sensitivity (10.14 LR+) when considering each night independently and 86% accuracy when averaging multi-night predictions. Conclusions This research demonstrates the feasibility of accurately detecting moderate-severe sleep apnea early in the stroke recovery process using wearable sensors and machine learning techniques. These findings can inform future efforts to improve early detection for post-stroke sleep disorders, thereby enhancing patient recovery and long-term outcomes. Clinical Trial SIESTA (Sleep of Inpatients: Empower Staff to Act) for Acute Stroke Rehabilitation, https://clinicaltrials.gov/study/NCT04254484?term=SIESTA&checkSpell=false&rank=1, NCT04254484