Background: Glucose intolerance is common in cystic fibrosis (CF), and is associated with worsening pulmonary function and nutritional status, and increased mortality. As sleep-disordered breathing is associated with disorders of glucose metabolism, it was hypothesised that recurrent episodes of hypoxaemia during sleep, and sleep disruption, would be associated with inflammation and glucose intolerance in CF. Methods: 25 children (aged 14±4 (mean±SD) years) with CF underwent polysomnography, actigraphy, measurement of serum inflammatory markers and oral glucose tolerance testing. Blood glucose area under the curve (AUC), as a cumulative measure of glucose response, was determined. Polysomnography data were compared with retrospective data from 25 healthy controls. Results: Forced expiratory volume in 1 s was 92±14% predicted. 24 subjects underwent glucose tolerance testing, of whom 29% had impaired glucose tolerance and 4% had diabetes. The mean nocturnal oxygen saturation correlated negatively with glucose AUC at 120 min (r=-0.49, p=0.015). Partial correlations and regression models including age, body mass index, nocturnal saturation and pulmonary function indicated that nocturnal saturation accounted for the majority of the predictive power for glucose AUC (R2=0.24, p=0.001). There were no meaningful relationships between sleep quality, inflammation and glucose tolerance. Conclusions: Lower oxyhaemoglobin saturation is associated with worse glucose regulation in children with CF. Further studies are needed to determine whether lower saturation negatively impacts glucose regulation or, alternatively, whether abnormalities in glucose metabolism are an early sign of pulmonary dysfunction.