Background: Problems such as the chronicity of the nature of multiple sclerosis (MS), the uncertain prognosis of the disease, the lack of definitive treatment, and the onset of the disease at a young age cause mental disorder, including depression, in MS patients. Objectives: Considering the prevalence of MS in Iran, this study was conducted with the aim of determining the prevalence of depression, disability and factors affecting it in patients with MS. Methods: In this cross-sectional descriptive study that was conducted in the group of patients with MS, 380 patients with MS were included in the study. The diagnosis of MS disease is based on physical examination, clinical symptoms and diagnostic tests that help the treating physician to definitively confirm MS disease. The tools used included demographic profile form, Beck depression questionnaire and EDSS disability tool. In this study, patients with MS in Ilam who referred to clinics and educational centers were included in the study. At first, the conditions of conducting the research were explained to the patients, and after explaining the objectives of the research to the patients in a language understandable to the patients and obtaining informed consent for the patients, the questioning began. Then the data from this study was entered into SPSS 16 software and data analysis was done using statistical tests. Results: Result showed, most of the patients in the study were male with a rate of 61.8%, in the age limit of 29 to 37 years with a rate of 48.9%, and a history of hospitalization with a rate of 67.1%. also result showed, 91(32.5) of patients were in normal depression level, 44(15.7) in mild depression level, 99(35.4) in moderate depression level and 46(16.4) in severe depression level. Also, mean (SD) depression score was 20.36 (12.77) and disability score was 3.35 (1.78). about relationship between disability and depression, result showed if the disability score increases, the depression score of the patients increases. Conclusions: Considering the high prevalence of depression and disability in patients with MS, it is necessary to carry out necessary interventions to reduce depression and disability in patients.