Multiple sclerosis (MS) is one of the central nervous system (CNS) diseases, which is chronic, inflammatory, and immune-mediated, typically presents in the third or fourth decade of life. 1,2 It is one of the most frequent nontraumatic disabling neurologic diseases, which affects 12,000 people in the United States alone per year. 3 There is high variability in the disease course. Its outcome is hard to predict, with no known cure. 4 Patients may be grouped into four categories; Relapsing-remitting (RR) MS, Secondary progressive (SP) MS, Primary progressive (PP) MS, and Progressive-relapsing (PR) MS, based on the course of the disease. 5 Nearly 87% of patients are of RRMS type, characterized by acute attacks (relapses) followed by partial or full recovery (remission). There are a heterogeneous group of symptoms, including changes in vision (unilateral visual loss, diplopia), weakness, incoordination, sensory loss or distortions, or changes in bowel and bladder function, cognitive change, fatigue, and mood disturbance. 6 Multifocal involvement of white and gray matter in the central nervous system can cause physical impairment and disability, with cognitive and psychological changes that often lessen patients' quality of life, occupational competence, and social interactions. 7 Psychiatric comorbidity is common in Background and objective: Multiple sclerosis is one of the chronic central nervous system diseases. Depression comorbidity is common with multiple sclerosis. This study aimed to determine the prevalence of depression among patients with multiple sclerosis and the relation of patient demographic data and disease status. Methods: A cross-sectional study was conducted in Rizgary Teaching Hospital in Erbil City, in a one-year duration from October 2017 to October 2018. The sample size was 169 known patients with multiple sclerosis, which was collected randomly. Beck Depression Inventory was used. The statistical package for the social sciences (version 25) was used for data analysis. Pearson Chi-square and Fisher's Exact Test were used to finding the association between various variables and depression. Results: The prevalence of depression among patients with multiple sclerosis was 53.5%. Age group more than 50 years was found more depressed (66.7 %,P = 0.006). Depression is more with those with multiple sclerosis for 10 years and more (84.6%) with a statistically significant association (P = 0.021). Treatment by rituximab show more depression (85.7%,P = 0.039). The frequency of severity of major depressive disorder was (mild 31.8%, moderate 52.9%, and severe 15.3%) and showed no significant association with different variables. Conclusion: The prevalence of depression among patients with multiple sclerosis was high. The age group of more than 50 years, duration of multiple sclerosis equal or more than 10 years, and rituximab treatment were regarded as risk factors.