BACKGROUND: Cystic fibrosis (CF) is characterized by chronic inflammation with increased oxidative stress. We evaluated the relationship between glucose tolerance and oxidative stress in CF children. METHODS: Patients 10-18 years old underwent oral glucose tolerance testing (n=31). At 2-h, we assessed blood glutathione and 4-hydroxynonenal-protein adducts (HNE-P), and urine 1,4-dihydroxynonane-mercapturic acid conjugate (DHN-MA). Plasma fatty acid (FA) profile was performed. Patients with impaired glucose tolerance (IGT) were retested 6 to 24 months later and received additional nutritional recommendations (NR) when possible. RESULTS: Fifty-two percent of patients had normal glucose tolerance (NGT), 42% IGT and 6% cystic fibrosis-related diabetes (CFRD). HNE-P concentrations significantly increased with diabetes (109%). Two-h BG correlated positively with HNE-P and negatively with DHN-MA. FA profile was modified with IGT. Of retested IGT patients, 25% received no NR; they remained IGT at 6 months and progressed to CFRD. Of those who received NR, 67% normalized, 11% remained intolerant and 22% developed CFRD. HNE-P levels dropped (88%) in IGT patients reverting to NGT, increased (94%) in the IGT patients with NR developing CFRD, decreased (90%) with persistent IGT. CONCLUSION: CF children showed evidence of increased oxidative stress with worsening of glucose metabolism. NR may delay the appearance of CFRD.