BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease involving brain and spinal cord. Weakness, cognitive impairment, pain, depression and fatigue, as common symptoms of MS, may significantly affect on general health of MS patients. This study aimed to investigate the influence of yoga and aerobic exercise on fatigue, pain, and psychosocial status among these patients. METHODS: In a randomized clinical trial study on 90 patients whom were randomly assigned to three equal groups of yoga exercises, aerobics exercises, and control group. The exercise program was performed as three sessions per week for 12 weeks. The exercise program included 40 minutes, including 5-10 minutes for warm-up, 25-30 minutes of exercise (walking), and 5 minutes for cooling down. Yoga exercises were scheduled three sessions a week for 12 weeks as well. RESULTS: There was no significant difference in fatigue, pain severity and psychological status among three groups prior to the study, but after the study, in yoga and exercise groups, fatigue physical function, physical and emotional role which patients play throughout daily life, social function, energy, mental status and overall hygiene increased, and the pain and fatigue were relieved in the patients. CONCLUSIONS: Yoga and aerobics exercise could decrease some of the MS symptoms, therapeutic costs, hospital stay, and days lost from work as well as increasing the patients' efficiency.