Abstract Background Fatigue is commonly reported by patients with inflammatory bowel disease [IBD], but the determinants of IBD-related fatigue have yet to be determined. Aims To identify the factors associated with fatigue in a large population of patients with IBD. Patients and Methods Fatigue and nine other IBD-related disability dimensions were assessed in a cohort of 1704 consecutive patients with IBD using the IBD-disk questionnaire in a cross-sectional survey of 42 French and Belgian centres. Fatigue and severe fatigue were defined as energy subscores >5 and >7, respectively. Determinants of fatigue were assessed using univariate and multivariate analyses (odds ratios [ORs] are provided with 95% confidence intervals). Results The prevalence rates of fatigue and severe fatigue were 54.1% and 37.1%, respectively. Both fatigue and severe fatigue were significantly higher in patients with active disease than in patients with inactive disease [64.9% vs 44.7% and 47.4% vs 28.6%, respectively; p < 0.001 for both comparisons]. In the multivariate analysis stratified by age, sex, type of IBD and IBD activity, fatigue was associated with age >40 years (OR = 0.71 [0.54–0.93]), female sex (OR = 1.48 [1.13–1.93]) and IBD-related sick leave (OR = 1.61 [1.19–2.16]), and joint pain (OR = 1.60 [1.17–2.18]), abdominal pain (OR = 1.78 [1.29–2.45]), regulating defecation (OR = 1.67 [1.20–2.32]), education and work (OR = 1.96 [1.40–2.75]), body image (OR = 1.38 [1.02–1.86]), sleep (OR = 3.60 [2.66–4.88]) and emotions (OR = 3.60 [2.66–4.88]) subscores >5. Conclusion Determinants of fatigue are not restricted to IBD-related factors but also include social factors, sleep and emotional disturbances, thus supporting a holistic approach to IBD patient care.