Background: The population of EGYPT has a significant Multiple sclerosis incidence recently with 1.4 % of all neurological disorders. As the latest edition of the Atlas of MS shows there are 2.8 million people living with MS around the world. The data released in 2020 indicated that almost 59.671 people are living with MS in EGYPT. This equates to one in every 1.500 people. Aim of the Work: The main target of our study was to assess the brain volume loss in MS patients and its significance. The secondary aim was to study the implications of the brain volume loss in different clinical aspects of the disease including disability, mood and cognition. Patients and Methods: This study was conducted upon 70 patients with RRMS as well as 30 healthy persons served as control group. Patients were diagnosed on clinical, laboratory and radiological imaging basis according to 2017 revised MacDonalds criteria. Results: There was a significant correlation between brain volume loss and disease duration. In controversy, there is no correlation found between the brain volume loss and EDSS scores of the study patients. There was a significant correlation between brain volume loss and cognitive function delay especially the verbal fluency and visuospatial aspects of cognitive evaluation. There was a significant correlation between disease duration and the language aspect of cognitive evaluation. There were no correlation between depression scores in our study patients and brain volume loss with the same results between depression scores and EDDS scores. Furthermore, there was a significant correlation between total cognition score testing and EDSS with also a significant correlation between the verbal fluency and EDSS. Conclusion: We described the effect of MS on the brain volume, cognitive functions and depression incidence by clinical and imaging methods. Since there is a high incidence in EGYPT which is well documented in the international medical scientific literature, hence MS evaluation should include brain volume loss BVL assessment with clinical cognition, depression and disease progression early detection in the Egyptian MS patients.