Fatigue is a common symptom of patients with chronic kidney disease, but seldom investigated after transplantation. We determined the prevalence, impact and related factors of severe fatigue in kidney transplant recipients (KTRs). Medical records and questionnaires were used to assess kidney function, donor characteristics, fatigue (Checklist Individual Strength), functional impairments (Sickness Impact Profile), work status, body mass index (BMI), pain, depressive symptoms, social support and sleeping problems in 180 participating KTRs. KTRs were compared with sex- and age-matched population-based controls. KTRs were significantly more often severely fatigued (39%) compared to matched controls (22%; P = 0.001). Severely fatigued KTRs had significantly more functional impairments than nonseverely fatigued recipients (effect size ≥ 0.7) P < 0.001, and less often a paid job (27% vs. 48%, P = 0.005). Univariate analysis showed that severely fatigued KTRs received more often a kidney from a deceased donor, had a higher BMI, more pain, discrepancy in social support, depressive symptoms and sleeping problems. In a multivariate analysis (n = 151) the latter two associations remained significant. Severe fatigue is a highly prevalent and disabling symptom in KTRs. Moreover, severe fatigue after kidney transplantation is more strongly related to behavioural and psychosocial factors than specific transplantation-related factors. Findings have implications for fatigue management.