Background: Multiple sclerosis (MS) is a chronic inflammatory central nervous system (CNS) disease, arising from a complex interaction of both environmental and genetic factors. MS affects individuals during the most productive time of their lives, and directly limits their work capacity, leading to major social and economic consequences. Objectives: The aim of the current work was to study neuropsychiatric manifestations in multiple sclerosis patients and to understand their correlation with the degree of clinical disability. Patients and Methods: A cross-sectional randomized study included a total of 40 consecutive M.S. patients (26 female and 14 males with mean age ± SD 32.60 ± 10.01) attended at MS Outpatient Clinics of Al-Azhar University Hospitals (Al Hussein and Bab Elshierya) and 20 controls during the period from January 2018 until February 2019. Results: The present study showed that there was a highly significant difference between patients and controls groups regarding Beck scale score for depression (p =0.005). There was 52.5% of MS patients had depression (while 25% of control subjects had depression). The study showed that there was significant positive correlation between beck scale score and EDSS scale score for disability a (p value =0.048 r=0.315). There was a highly significant difference between patients and control group regarding Hamilton scale score for anxiety as (P-value = 0.002). Conclusion: An understanding of neuropsychiatric disorders in MS is important for all professionals involved in the care of people with MS. These disorders affect about half of patients.