IntroductionMultiple sclerosis (MS) is a chronic autoimmune disorder that affects the central nervous system characterized by demyelinating lesions that are disseminated in space and time. Depression is a common symptom in MS, and the pathogenesis is multifactorial. In Saudi Arabia, there is limited current literature about the incidence and relationship between depression and MS. This study is an attempt meant to address the point prevalence of depression, risk factors, and relationship to disease-modifying therapy. In addition, we describe several clinical, nutritional, and social aspects of MS. MethodsA descriptive cross-sectional study was conducted in Jeddah, Saudi Arabia. The target sample in this study consisted of patients in Saudi Arabia with MS. Data collected included a depression questionnaire based on PHQ9, compliance on therapy, the preferred therapy, and the impact of the disease on daily activity and economic state. ResultsA total of 341 Saudi MS patients were enrolled in the present study. The gender distribution showed that 65.4% (n=223) of the study population were females. The mean age of the patients was 34.80±9.907 years. Most of the patients who were included in this study (95.6%) had depressive symptoms in variant levels. Variable changes in depression levels were detected in both genders specifically moderate depression was most common in males (33%) while females had moderately severe depression (38%). Numbers of relapses, future vision, and changes in workout were associated with statistically significant depression levels. ConclusionDepressive symptoms are common in patients with MS. Although all disease-modifying therapies are available in Saudi Arabia, MS clinics with multidisciplinary care are not yet efficiently activated. Nonpharmacological interventions such as smoking cessation, exercise, and psychological health should be part of the management of any patient with MS.