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Objectives: To study the severity and 5-year course of fatigue in patients with late-onset sequelae of poliomyelitis (LOSP) and to identify physical and psychosocial determinants of fatigue., Design: Prospective cohort study with 5 measurements over 5 years., Setting: University hospital., Participants: Patients with LOSP (N=168); 89% of the subjects completed the study., Interventions: Not applicable., Main Outcome Measures: Fatigue assessed with the Fatigue Severity Scale (FSS). Potential determinants were perceived physical functioning, bodily pain and mental health, extent of paresis, walking capacity, comorbidity, sleeping disorders, coping, and social support. Associations were investigated by multivariable longitudinal analysis using generalized estimating equations., Results: The mean FSS score ± SD at baseline was 5.1±1.4, which did not change significantly during the 5-year follow-up. Reduced physical functioning, increased bodily pain, reduced sleep quality, more psychologic distress, and higher task-oriented coping were independently associated with fatigue. The extent of paresis and walking capacity were strongly associated with physical functioning., Conclusions: Fatigue is severe and persistent in patients with LOSP due to physical and psychologic factors, which has implications for counseling and treatment. In addition to the commonly applied interventions targeting physical aspects, psychologic interventions are a potential area for reducing fatigue., (Copyright © 2011 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)