BACKGROUND: There has been little investigation of fatigue, a common symptom in inflammatory bowel disease (IBD). The aim of this study was to evaluate fatigue more comprehensively, considering relationships with psychological and biological factors simultaneously in a population-based IBD community sample. METHODS: Manitoba IBD Cohort Study participants (n = 318; 51% Crohn's disease [CD]) were assessed by survey, interview, and blood sample. Fatigue, sleep quality, daytime drowsiness, stress, psychological distress, and quality of life were measured with validated scales. Hemoglobin (Hg) and C-reactive protein (CRP) levels were also obtained. Differences were tested across disease activity and disease subtype. RESULTS: Elevated CRP was found for 23% of the sample and 12% were anemic; 46% had active disease. Overall, 72% of those with active and 30% with inactive disease reached clinical thresholds for fatigue (Multidimensional Fatigue Inventory; P < 0.001); 77% and 49% of those with active or inactive disease, respectively, experienced poor sleep (P < 0.001). There were few differences between those with CD and ulcerative colitis (UC) on the factors assessed, except for higher CRP levels in CD (mean 8.8 versus 5.3, P < 0.02). Multiple logistic regression analyses found that elevated fatigue was associated with active disease (odds ratio [OR] 4.2, 95% confidence interval [CI] 2.2-7.8), poor sleep quality (OR 4.0, 95% CI 1.9-8.6), and perceived stress (OR 4.2, 95% CI 2.2-8.1), but not with hours of sleep, Hg, or CRP. CONCLUSIONS: Fatigue and poor sleep are not only highly prevalent in active disease, but both are still significant concerns for many with inactive disease. Psychological factors are associated with fatigue in IBD in addition to disease and sleep considerations.