Fatigue, reduced quality of life (QOL), and lower physical activity levels are commonly reported in patients with multiple sclerosis (MS). This study evaluated the effects of elliptical exercise on fatigue and QOL reports in patients with MS. Patients with MS (n = 26) completed the Fatigue Severity Scale (FSS), the Modified Fatigue Impact Scale (MFIS), and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) before and after completing 15 elliptical exercise training sessions. Changes in fatigue and QOL were assessed based on any changes in the fatigue and SF-36 questionnaires, and correlations between changes in each of the scales were made to determine whether a relationship was present between the fatigue and QOL measures. Results showed significant improvement in FSS, MFIS, and five SF-36 subscales as a result of elliptical exercise. The change in FSS correlated with change in two of the SF-36 subscales. Elliptical exercise for patients with MS results in significant improvements in both fatigue and QOL. These findings indicate that regular elliptical exercise could be a part of inpatient and outpatient MS rehabilitation programs.