OBJECTIVE - Although cystic fibrosis–related diabetes (CFRD) is associated with decreased lung function, sex is not known to influence CFRD. However, compared with male subjects with cystic fibrosis, female subjects with cystic fibrosis have increased morbidity. This study examines the association between female subjects with CFRD and poor lung function relative to male subjects using the percent predicted forced expiratory volume in 1 s (FEV1) as a surrogate measure of morbidity. RESEARCH DESIGN AND METHODS - We compared 323 patients with established CFRD with 489 cystic fibrosis control subjects with normal glucose tolerance (NGT) listed in the U.K. Cystic Fibrosis Database. Patients stratified by sex and chronic Pseudomonas aeruginosa infection were compared using binary logistic regression, and patients with new CFRD diagnoses were compared prospectively for the year 2002. RESULTS - CFRD in female subjects (but not male subjects) without chronic P. aeruginosa infection had a 20% lower percent predicted FEV1 compared with control subjects with NGT (95% CI -11.7 to -27.7; P < 0.0001). Genotype, age, treatment center, age at diagnosis of cystic fibrosis, pregnancy, liver function, or dose of pancreatic enzyme replacement therapy did not confound this female disadvantage. Comparison of female subjects with newly diagnosed CFRD free of chronic P. aeruginosa infection with matched control subjects with NGT showed no FEV1 disadvantage in the 1st year after CFRD diagnosis. CONCLUSIONS - Only female subjects with CFRD have significantly decreased lung function compared with sex-matched NGT control subjects. The absence of poor lung function in the first 12 months after diagnosis of diabetes suggests that an opportunity may exist to intervene and possibly prevent a decline in lung function, which can be as much as 20% in female subjects with CFRD.