['To determine whether there is a relationship between self-reported fatigue and the energy cost of walking (ECw), and how self-reported fatigue and ECw relate to physical functioning in patients with multiple sclerosis (MS).', 'Cross-sectional cohort study, using structural equation modeling.', 'Home environment and at a university medical center.', 'Patients (N=75) were obtained from a longitudinal study on outcome measurement and functional prognosis in early MS. Patients were included if they were able to walk for 6 minutes without being assisted by a person. The age range was between 28.0 and 69.7 years and the median Expanded Disability Status Scale was 2.5 (range, 1.0-6.5).', 'Not applicable.', 'Self-reported fatigue was measured with the Fatigue Severity Scale, the vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and a visual analog scale. Physical functioning was determined with the physical functioning subscale of the SF-36, fast walking speed, and comfortable walking speed. The ECw (J·kg(-1)·m(-1)) was measured with the energy cost of the walking test.', 'The relationship between ECw and latent variable fatigue had a β=-.188 (P=.236), that between ECw and physical functioning (SF-36 physical functioning) had a β=-.344 (P=.001), and that between fatigue and physical functioning had a β=-.448 (P=.000).'] Are self-reported fatigue and energy cost during walking related in patients with multiple sclerosis?