Background: Lemborexant (LEM), a dual-orexin-receptor-antagonist approved to treat adults with insomnia, increases total sleep time (TST) and rapid eye movement (REM) sleep. Patients with obstructive sleep apnea (OSA) or co-morbid insomnia and OSA (COMISA) report sleeping difficulties and reduced REM, therefore sleep architecture was analyzed during LEM treatment. Methods: Study E2006-G000-304 (NCT02783729) was a 1-month, randomized, double-blind, placebo (PBO)- and active-comparator zolpidem-ER 6.25mg (ZOL)-controlled study in adults ≥55y with insomnia disorder. Subjects received PBO, LEM 5mg (LEM5), 10mg (LEM10), or ZOL. Least-square-mean duration of each sleep stage (minutes) was compared from pooled data on Nights (NT)1/2 and NT29/30 for mild OSA subjects (apnea hypopnea index ≥5 to <15 events/h). Treatment-emergent adverse events (TEAEs) were recorded. Results: Of 409 subjects with mild OSA (LEM5=114/LEM10=105/ZOL=112/PBO=78) change from baseline (CFB) in TST and REM sleep was significantly larger with both LEM doses versus ZOL/PBO on both nights. CFB for total nonREM sleep was significantly higher (P<0.0001) with both LEM doses versus PBO on both nights. LEM5 showed significantly higher (P<0.05) nonREM sleep versus ZOL at NT29/30. Most TEAEs were mild/moderate. Conclusions: LEM significantly increased TST, REM, and nonREM sleep versus PBO in subjects with insomnia and mild OSA. Data support LEM treatment in the COMISA population.