Background: Multiple sclerosis is a chronic disease that affect all aspects of the patients’ life causing multiple progressive symptoms; most common fatigue which leads to dependency of patients on their family for carrying out their daily routine activities. Aim: The present study aims at evaluating the effect of an educational program on fatigue level among multiple sclerosis patients. Design: A quasi-experimental one-group pretest-posttest was used. Setting: the study was conducted in multiple sclerosis outpatient clinic in El-Kasr El-Eini University Hospital. Sample: A convenient sample of (250) multiple sclerosis patients. Tools: Two tools were used: first tool was Structured MS patient dietary knowledge questionnaire, second tool was The Arabic Version of Modified Fatigue Impact Scale. Results: Showed a highly statistical negative correlation between dietary knowledge and cognitive, psychosocial fatigue among MS patients in pre, post and 3 months after implementation of the program. Conclusions: The results of this study indicated that MS patients' dietary knowledge improved after application of the educational program as well as there was a decline in MS patients' fatigue level with statically significance differences between pre, post and 3 months after application of the program. Recommendation: Dissemination of dietary knowledge program among other multiple sclerosis patients. Keywords: Multiple sclerosis patients, dietary knowledge, fatigue