Rationale: Sickle cell disease results in significant morbidity and mortality attributable to pulmonary complications. The pattern of lung function change across childhood in sickle cell disease is not well delineated. Objectives: To determine if the pattern of lung function in sickle cell disease differs from race matched predicted values across childhood, to describe that pattern of change and to examine the effect of clinical covariates on lung function. Methods: Lung function measurements for children with sickle cell disease aged 8-18 years from a single centre were examined for inclusion. Mixed model analysis was used to retrospectively review lung function in these children in comparison with those predicted by race-matched reference equations. The contribution of age, gender, hemoglobin level, and beta-globin genotype on longitudinal changes in lung function was examined. Results: Children with sickle cell disease show significant decline in spirometric lung volumes across childhood which are concordant with the pattern of change in other measures of lung volume. The average decline for forced expired volume in 1 second and total lung capacity is 2.93% and 2.15% predicted/year for males and 2.95% and 2.43% predicted/year for females. Beta-globin genotypes known to be associated with more severe disease showed a faster decline in lung function while gender showed an inconsistent effect on lung function. Conclusions: Lung volumes in children with sickle cell disease decline with age. The pattern of decline begins in childhood and supports a predominately restrictive defect.