Fatigue is considered as the most revealed symptoms in multiple sclerosis patients, reported by 88% of patients and has significant impact on all stages of life such as altering in daily living activity or psychosocial/mental functions. The pathogenesis of fatigue remain poorly understood and how its impact on self-management. The aim of study was to assess fatigue and self management among multiple sclerosis patients. A quantitative descriptive correlational design was used in this study. The study was conducted at both King Abdulaziz University Hospital and King Fahad Armed Forces Hospitals in Jeddah City from January till March 2018, data collected from outpatients' clinic and Inpatients' medical-wards. A convenience sample of 50 Multiple Sclerosis patients. Data was collected through the main one tool, it consists of three parts; Part I, Socio-demographic and clinical data constructed by the researchers. Part П, Modified Fatigue Impact scale; to assess the Impact of fatigue on physical, cognitive, and psychosocial functioning in patient with Multiple Sclerosis.. Part ПІ, Multiple Sclerosis Self Management Scale Revised; to provide a multidimensional and psychometrically assessment of self-management knowledge and behavior among Multiple Sclerosis patients. The study results showed there was a statistically significant negative correlations between fatigue subscales and overall self-management among Multiple Sclerosis patients with p-value (.019). Also, there was a statistically significant negative correlations between self-management factor scales and overall fatigue among Multiple Sclerosis patients with p-value (.019). It was concluded that there was a negative correlations between overall fatigue and overall self-management among Multiple Sclerosis patients, whenever fatigue severity increases, self-management decreases. It was a recommendation to encourage governmental policy and other decision makers in the Saudi community to develop periodically structure health education training program regarding self-management in MS and provide appropriate environments or facilities to conduct such programs, where nurses play a key role through health education and cooperate with other health care system.