BACKGROUND & AIMS: Fatigue profoundly impacts quality of life and is a common complaint among patients with chronic disease. This study examined the degree of fatigue and health-related quality of life (HRQOL) in children with inflammatory bowel disease (IBD). METHODS: Seventy children with IBD and 157 healthy controls and their parents completed age-appropriate measures of fatigue (PedsQL Multidimensional Fatigue Scale) and HRQOL (PedsQL 4.0 Generic Core Scales). Children with IBD completed the IMPACT III Quality of Life Questionnaire, and the Children's Depression Inventory: Short form was completed by children with IBD and healthy controls. Disease activity was determined according to the diagnosis with either the Pediatric Crohn's Disease Activity Index (PCDAI) or a Physician's Global Assessment. RESULTS: Children with Crohn's disease (N = 52) had a median PCDAI of 0, and 56% with ulcerative colitis (N = 13) or indeterminate colitis (N = 5) were in remission. Mean child self-report PedsQL Multidimensional Fatigue Total Scale scores were 73.9 +/- 16.8 and 82.2 +/- 12.3 for patients with IBD and controls, respectively (P < .001). Mean child self-report PedsQL 4.0 Generic Core Total Scale scores were 76.7 +/- 14.2 and 85.9 +/- 10.4 for patients with IBD and controls, respectively (P < .0001). Children with IBD did not self-report statistically different mean total fatigue and subscale scores compared with children with rheumatologic diseases or cancer. CONCLUSIONS: In children with primarily inactive IBD, fatigue was significantly higher and HRQOL was significantly lower than in healthy controls. Results among children with IBD were comparable to children with rheumatologic diseases and cancer.