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Background: Risk factors for childhood stroke differ significantly from those in adults. Obstructive Sleep Apnea (OSA) is an independent risk factor for adult stroke. Children with Sickle Cell Disease (SCD) have a higher prevalence of OSA than the general pediatric population, and nocturnal hypoxemia in these patients is independently predictive of future CNS events. Hypoxemia and hypercapnia secondary to OSA result in a pro-inflammatory and prothrombotic cascade associated with metabolic dysregulation and endothelial dysfunction.Hypothesis: We hypothesized that OSA, hypoxemia and/or hypercapnia are associated with an increased stroke risk in a pediatric population.Methods: Clinical and radiologic data of consented children seen in the stroke program from 1992-2014 with clinically indicated sleep study/polysomnography (PSG) were retrospectively reviewed and analyzed.Results: Thirty-one children (31/947; 14 male, mean age at PSG 8.4 years) were identified. Twenty-three children had arterial ischemic stroke (AIS) (mean age 7.6 years, SEM 0.99 years) and eight were non-stroke arteriopathy patients (mean age 10.5 years, SEM 1.16 years). Children diagnosed with AIS had significantly higher prevalence of OSA than children with no stroke (69% vs. 25%, p=0.0429) regardless of the timing of sleep study (11/15, 73.3% OSA post-stroke diagnosis and 5/8, 62.5% OSA pre-stroke diagnosis). AIS patients had significantly lower minimum SaO2 values overnight (83.19% vs. 94.56%, p=0.0072), and higher overnight mean end tidal (et) and transcutaneous (tc) CO2 levels (et CO2 42.78 vs. 41.75 mmHg, p=0.4940; tc CO2 42.08 vs. 39.67 mmHg, p=0.3544). Primary risk factors of AIS in children with clinically indicated PSG included 3 moyamoya (33% with OSA), 8 cardiac (63% with OSA), 5 SCD (83% with OSA), and 7 other (86% with OSA). Cardiac patients had the lowest nocturnal SaO2 and highest CO2 levels when compared to moyamoya, SCD and others.Conclusions: In our study, children with AIS were more likely to have OSA and nocturnal hypoxemia, highlighting these as potential risk factors for stroke in childhood. Future prospective studies are required to explore the relationship between stroke, hypoxemia and hypercapnia.