Multiple sclerosis (MS) is the most prevalent central nervous system demyelinating disease. There are known risk factors for MS. However, there is uncertainty in its protective factors. Few studies have demonstrated that some chronic infections may have protective effects on this disease. We carried this study to investigate the relation between Helicobacter pylori (HP) infection and the prevalence and severity of MS. In this case-control study, 163 MS patients and 150 sex- and age- matched controls were included. Blood samples for IgG and IgM anti HP antibodies were collected from all individuals. Also, the Expanded Disability Status Scale (EDSS) was used to evaluate the MS patients. Suitable statistical analysis was applied. A Significant difference was observed in seropositivity between these two groups (P<0.001) but no significant difference was seen in seropositivity between conventional and opticospinal MS (P=0.522). No significant difference was observed in seropositivity among ages (P=0.075) and between genders (P=0.204). A significant difference was seen in EDSS value between seropositive and seronegative patients (P=0.017). We concluded that patients with HP infection had lower incidence of multiple sclerosis and MS patients with HP infection showed lower neurologic complications, which can demonstrate that HP infection may have a protective influence on MS pathogenesis.