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Background: Medically unexplained physical symptoms (MUPS) are highly prevalent, frequently co-occurring with psychiatric symptoms such as depression, alexithymia, and anxiety. Objective: To evaluate the relation between depression, anxiety, and alexithymia and severity of somatic symptoms in patients with MUPS. Method: This is a cross-sectional study conducted on 196 patients suffering from MUPS. The patients were recruited from tertiary care internal medicine and neuropsychiatry clinics during the first quarter of 2019. The Patient Health Questionnaire (PHQ-15), (PHQ-9), Generalized Anxiety Disorder (GAD-7), Structured Clinical Interview for DSM-IV Axis I Disorders Clinician Version (SCID-I-CV), and Toronto Alexithymia Scale (TAS-20) were employed to assess somatic severity, depression, anxiety, major mental disorders, and alexithymia in the sample of patients. Results: The results of the study indicate that GAD-7 and PHQ-9 scores had a positive correlation with PHQ-15 ( p < 0.05) in multivariate regression. In contrast, TAS-20 was not independently correlated with PHQ-15. Adding TAS-20 to GAD-7 and PHQ-9 in the equation of the regression model enhances the predictive capacity of the model ( p < 001). Conclusion: The results of the study indicate that only anxiety and depressive symptoms, but not alexithymia, were associated independently with MUPS severity.