Objectives: To evaluate the prevalence of major depression disorder in Iraqi patients with systemic sclerosis (SSc) and its relationship with disease severity. Patients and methods: This case-control study involved 50 patients who have SSc according to the criteria developed by the 2013 American College of Rheumatology/European League Against Rheumatism. Demographics and clinical data was collected based on different variables. Disease severity for SSc was assessed with the scleroderma assessment questionnaire (SAQ). Medications used, and autoantibody profile were recorded. Depression was diagnosed using Diagnostic and Statistical Manual of Mental Disorders-5 (DSM5). Results: The prevalence of major depression disorder was 44% compared to control 2.0%, in which major depression disorder 39.3 folds associated with SSc patients compared to control. Furthermore, cases with a severe form of disease evaluated by SAQ had higher rate of depression. The major depression disorder was significantly correlated with smoking. SSc cases with higher education (college) had the highest rate of major depression disorder (36.4%) compared to a rate between 13.6% and 27.3% for lower level of educational attainment. The risk of having major depression disorder was not different in variables and had no obvious or statistically significant association with major depression disorder. The presence of autoantibodies (anti centromere and anti Scl70 antibodies) had no important or statistically significant effect on the presence of major depression disorder. Conclusions: The prevalence of major depression disorder in SSc patients was significantly higher in patients than in controls. SSc disease severity increase major depression disorder rate.