Background: The frequency and the perceived intensity of life stressors, coping strategies, and social supports are very important in everybody′s well-being. This study intended to estimate the relation of irritable bowel syndrome (IBS) and these factors. Materials and Methods: This was a cross-sectional study carried out in Isfahan on 2013. Data were extracted from the framework of the study on the epidemiology of psychological, alimentary health, and nutrition. Symptoms of IBS were evaluated by Talley bowel disease questionnaire. Stressful life event, modified COPE scale, and Multidimensional Scale of Perceived Social Support were also used. About 4763 subjects were completed questionnaires. Analyzing data were done by t-test and multivariate logistic regression. Results: Of all returned questionnaire, 1024 (21.5%) were diagnosed with IBS. IBS and clinically-significant IBS (IBS-S) groups have significantly experienced a higher level of perceived intensity of stressors and had a higher frequency of stressors. The mean score of social supports and the mean scores of three coping strategies (problem engagement, support seeking, and positive reinterpretation and growth) were significantly lower in subjects with either IBS-S or IBS than in those with no IBS. Multivariate logistic regression revealed a significant association between frequency of stressors and perceived intensity of stressors with IBS (odds ratio [OR] =1.09 and OR = 1.02, respectively) or IBS-S (OR = 1.09 and OR = 1.03, respectively). Conclusions: People with IBS had higher numbers of stressors, higher perception of the intensity of stressors, less adaptive coping strategies, and less social supports which should be focused in psychosocial interventions.