Background: Multiple sclerosis (MS) is a chronic autoimmune neurological illness that has a significant influence on an individual's, family's, and society's health-related quality of life. Aim: To identify the burden of Multiple Sclerosis and its impact on patients quality of life. Subjects and methods: This study was a cross-sectional study, carried out in the neurology department, Zagazig university hospitals and Al-Mabara medical insurance hospital, Zagazig. The study was carried out from January 2020 to December 2020 on 60 MS patients diagnosed according to the Revised McDonald criteria. Detailed history was taken from all participants. Complete general and neurological examinations were performed. Disability was assessed using Kurtzke Expanded Disability Status Score (EDSS). Cognitive function was assessed using the Arabic version of the Montreal cognitive assessment (MoCA) scale. A self-related Health Status Questionnaire was implemented. Work performance related to physical, cognitive, and psychological dimensions was studied with the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23). Results: MS patients with more disability (EDSS more than 3.5) have statistically significant cognitive impairment according to MoCA score (P = 0.001) and have also high statistically significant increase in workplace problems according to MSWDQ-23 score than those with EDSS less than 3.5 (p < 0.001). Conclusion: There is a substantial impact of MS on patients' QOL, owing to the patients' psychological and physical conditions, as well as the unfavorable influence on work conditions.