Purpose: To examine whether general fatigue and fatigue during or after walking are related to energy demands during walking and physical fitness in children and young adults with physical disabilities. Methods: Sixty-eight individuals with physical disabilities participated. General fatigue (Checklist Individual Strength [CIS8R] questionnaire), walking-induced fatigue (OMNI [OMNIwalk] scale after walking for 6 min), gross and net energy costs (ECs) of walking, physical strain of walking, and aerobic and anaerobic fitness were measured. Results: Regression analyses showed no relations with the CIS8R. For all participants, a higher net EC was weakly related to an increased OMNIwalk. For teenagers only, low anaerobic fitness and high physical strain of walking values were moderately related to high OMNIwalk scores. Conclusion: Low anaerobic fitness and high physical strain values partly explain fatigue after walking in teenagers with cerebral palsy, but not in younger children. General fatigue was not explained by low fitness levels or high energy demands of walking.