Background: Multiple Sclerosis (MS) is an unpredictable autoimmune disease that causes damage to the central nervous system including brain, spinal cord and optic nerve. This damage occurs as the body's immune system attack the protective coating called myelin around nerve fibers in the central nervous system. It can affect different aspects of a person's physical and cognitive functioning. Multiple Sclerosis is a complex, chronic disease that necessitates the support of a knowledgeable and concerned team of healthcare providers. This study aimed to assess the relation between upper extremity motor function among patients with MS with fatigue and cognitive impairment. Descriptive correlational research design was conducted on sixty adult patients with the diagnosis of MS who were admitted the MS Outpatient Clinic of El-Hadara Hospital in Alexandria. Four tools were used for collecting data: Tool I: Demographic and clinical data tool, tool II: Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, tool III: Multiple sclerosis Neuropsychological screening questionnaire, and Tool IV: Fatigue assessment tool. Results of the present study revealed that moderate disability of the upper extremity was the most disability level encountered representing more than one third among the study sample (36.7%) , furthermore; more than two third (73.3%) the study sample often having cognitive problems, suffering from severe fatigue (36.7%) and fatigue partially interfered with their quality of life(46.7%). Additionally, there was no significant relation between studied patients' motor function of upper extremity and their cognitive function p=0.54. On the other hand, there was a significant relation between studied patients' motor function of upper extremity and fatigue severity level, and effect of fatigue on their quality of life. Accordingly, conducting a comprehensive assessment of patients' upper extremity motor function, cognitive function, and fatigue level among patients with MS is necessary to determine the degree of suffering; this will help the nurses to predict their functional status and the effect of MS on their quality of life.