Objective: Irritable bowel syndrome (IBS) is associated with alterations in the gut-brain axis which influences various gastrointestinal and psychological functions. The cognitive performance and frequency of depression have not been previously assessed among Saudi patients with IBS so the primary aim was to study cognitive functions and depression in patients with IBS. Methods: This cross-sectional study enrolled Saudi males and females of more than 18 years of age living in Riyadh and Kharj cities, Central Region, Kingdom of Saudi Arabia. Participants were invited to complete 2 self-administered validated questionnaires. One questionnaire focused on Rome III criteria which classify functional GI disorders (FGIDs) in addition to the Patient Health Questionnaire (PHQ-9) which includes a set of 3 self-report scales designed to measure the major depressive disorder. Individuals who did not show IBS criteria have been enrolled as control subjects. Results: The overall prevalence of IBS among the enrolled subjects was 17.3% of whom women constituted (73.4%). Among subjects with IBS, 71.3% had mixed (constipation and diarrhea) type, 5.3% had diarrhea predominant type and 23.4% had constipation predominant IBS. Depression was significantly higher in IBS patients compared to control subjects. Among IBS cases, 20.2% had minimal depressive symptoms and 20.2% had major depression, mild severity. Major depression with moderate severity was found in 18.1% and major depression with severe severity was found in 28.7%. Depression was associated with impaired cognitive function in 25% of IBS patients. Conclusion: IBS was associated with depression and mild impairment of cognitive functions. The frequency of depression in IBS subjects suggests the importance of the psychological assessment of these patients and the integration of cognitive therapy with pharmacologic IBS therapy.