Background <p>Many studies discovered that psychiatric comorbidities such as depression, anxiety and cognitive impairment (CI) are common in MS (multiple sclerosis) and have a deleterious effect on MS outcome, in comparison to general population. Aim of our study is to determine the frequency of anxiety, depression and cognitive impairment (CI) in RRMS (relapsing –remitting multiple sclerosis) patients in Upper Egypt as a part of Middle East and North Africa (MENA) region and predictors of these comorbidities.</p> Results <p>A cross sectional study was conducted on 100 RRMS patients. Demographic and clinical data were collected prospectively. Hamilton Anxiety scale (HAM-A), Hamilton Depression scale (HAM-D) and Brief International Cognitive Assessment for MS (BICAMS) scales were applied to determine frequency of anxiety, depression and CI, respectively. Binary logistic regression was applied to determine the predictors of these comorbidities. Roc curve analysis was performed to determine the cutoff values. Sixty-two patients (62%) were female with a mean age 33.52 ± 9.75 and range age 18–58 years. Frequency of anxiety, depression and CI were 19%, 44%, 66%, respectively. EDSS (Expanded Disability Status Scale) was the only predictor of anxiety and depression with cutoff value 3.5 on EDSS scale. EDSS and number of MS attacks were the predictors of CI, with cutoff value 3 on EDSS scale and three attacks, respectively.</p> Conclusion <p>Psychiatric and cognitive comorbidities with MS are more prevalent when EDSS ≥ 3.5 and ≥ three MS attacks, respectively. Combined screening with psychosocial assessments may improve the accuracy of detection. Future studies should validate these cutoff values in diverse MENA cohorts and assess whether early psychiatric intervention alters disability trajectories and improve the quality of life in these chronic patients.</p>