Fatigue is the most common symptom of multiple sclerosis (MS). This study aimed at comparing the effect of immunomodulators and immunesuppressants on fatigue in MS. The study included 35 MS patients (26 patients on immunemodulators and 9 patients on immunosuppressants). All patients underwent clinical assessment and evaluation of fatigue, depression, cognition and ambulation. Results revealed that fatigue is significantly correlated positively with depression, ambulation and disability while depression is correlated positively with ambulation and cognition is correlated with disability.The more fatigued the patient is, the more depressed, disabled and less ambulant he becomes.The more depressed the patient is he becomes more cognitively impaired and less ambulant.