Background <p>Glucose tolerance abnormalities are common in cystic fibrosis (CF). However, there is a paucity of data describing glucose intolerance in children with CF and its impact on health-related quality of life (HRQOL). This study aimed to explore the relationship between abnormal glucose tolerance (AGT) and HRQOL in children with CF as well as the degree of disease severity.</p> Methods <p>This cross-sectional study was conducted on 6–13-year-old children attending CF clinics with their parents. Clinical assessment, oral glucose tolerance test (OGTT), and sputum culture evaluation were performed for all patients. HRQOL was measured using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) (child and parent versions). Disease severity was assessed using the Shwachman-Kulczycki score and lung function. The impact of OGTT results on HRQOL and parameters of disease severity was assessed.</p> Results <p>Fifty patients with CF and their caregivers completed the survey. 24% of children were found to have AGT. 76% had normal glucose tolerance (NGT). Children with AGT had reduced HRQOL, more healthcare utilization, and higher disease severity than those with NGT. Moreover, there were strong relationships between the CFQ-R child-reported social functioning, total score, and glucose intolerance (<i>P</i> = 0.003,0.002). Additionally, parents’ reported treatment burden and school performance were significantly lower among the AGT group (<i>P</i> = 0.035, 0.007).</p> Conclusions <p>This study signifies that children with CF with glucose intolerance may have unfavorable QOL, worse clinical status, and lower lung function. Additional research addressing effective strategies for early diagnosis and treatment of AGT in children with CF may improve the HRQOL of this patient population.</p>