Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Current research into potential causes, risk factors, and treatment is largely based around the immune response involved in the pathophysiology of the disease, including factors that contribute to the augmentation of this immune response. This review aimed to determine the role of sodium as a risk factor for increased autoimmunity and inflammation in relation to MS pathogenesis. This systematic review searched the Scopus, MEDLINE, and PubMed scientific databases for studies related to MS and sodium. Studies were included if they addressed sodium intake and MS but were not limited to a disease type or to a study design. Study quality was assessed through the use of the quality rating checklist of the Academy of Nutrition and Dietetics. A total of 12 studies were included in the review, including human, animal, and cellular studies. The studies related to the proinflammatory effect of sodium, the blood-brain barrier, and an effect on autoimmunity. The data presented throughout this review provide insight into the emerging evidence base for sodium intake as a risk factor for MS disease progression and potentially onset of disease. More studies are needed to determine if the influence of sodium is as a single nutrient or has a combined effect as part of an overall eating pattern. This review was registered at PROSPERO as CRD42016039174.