OBJECTIVE: Fatigue is common among patients with Inflammatory Bowel Disease (IBD). Pro-inflammatory cytokines are elevated in chronic inflammation and can induce "sickness behaviors", such as fatigue. Chronic inflammatory states also lead to growth hormone (GH) resistance, demonstrated by low levels of Insulin-like Growth Factor (IGF-1) and elevated GH. This study evaluated the relationship between IGF-1, pro-inflammatory cytokine levels and fatigue in patients with IBD. METHODS: This prospective study of children with IBD, ages 10-16 years, were recruited from a sub-specialty ambulatory clinic. Participants and their parents completed age-appropriate generic and disease-specific health related quality of life (HRQOL) instruments. Serum samples obtained at the same encounter were analyzed for Th17 cytokine and IGF-1 levels. HRQOL scores were compared to a healthy sample and HRQOL scores and cytokine levels were compared by IGF-1 z-score quartiles. RESULTS: 67 IBD patients were recruited, median age of 13.7 years (IQR, 11.7-15.3). 48 (72%) had inactive disease based on Physician Global Assessment. IBD patients reported lower generic HRQOL (p = 0.0006) and more fatigue (p = 0.0004) than a healthy sample. Patients with IGF-1 z scores in the lowest quartile had significantly lower disease-specific HRQOL (p = 0.01) and more fatigue (p = 0.02) than the remainder of the cohort. Serum IL-10, IL-17A, IL-6, Interferon-gamma were significantly higher in IBD patients with IGF-1 z scores in the lowest quartile (p < 0.05). CONCLUSIONS: Children with sub-clinical IBD experience more fatigue and lower generic HRQOL than healthy children. Lower IGF-1 z scores are associated with more fatigue, and this relationship may be mediated through pro-inflammatory cytokines.