Irritable Bowel Syndrome (IBS) is the most prevalent functional gastrointestinal disorder. Psychosocial stress is one of the pathogenic factors involved in the pathogenesis of IBS. The Pressure Management Indicator (PMI) is a validated questionnaire to analyze all aspects of occupational stress-a model involving sources of pressure, the mechanisms of coping, the personality, and the resulting effects of the interaction between these 3 elements. The purpose of this study was to analyze the association between socio-professional stress effects in IBS, and the relationship of IL-6 levels and salivary cortisol with occupational stress.We conducted a prospective cross-sectional study on 76 patients (39 patients with IBS, diagnosed according to the Rome III criteria and 37 healthy controls) who were investigated using a validated self-administered questionnaire: PMI. The biologic markers of chronic stress were analyzed using salivary cortisol and the immune response with serum interleukin 6 (IL-6).The IBS patients corresponded to the following subtypes: diarrhea-predominant: 22, constipation-predominant: 14 and mixed: 3. All the socio-professional pressure effects variables and scales were statistically significant, in an inversely proportional relation with IBS. Lower scores (poor effects) were found in IBS subjects. The adjusted odds ratios of having IBS versus healthy subjects for the socio-professional pressure effects scales were: 0.81 (95% confidence interval (CI) 0.72-0.88), for satisfaction, 0.85 (95% CI 0.78-0.91) for organization, 0.85 (95% CI 0.79-0.91) for mental wellbeing and 0.8 (95% CI 0.71-0.87) for physical wellbeing (P <.001). Also, the serum IL-6 levels were significantly higher in IBS than in controls (p < 0.001). There was no statistical difference between the salivary levels of cortisol between IBS patients and controls (P = .898).The level of occupational stress was higher in IBS patients compared to healthy subjects (socio-professional stress effects were lower in IBS patients) and correlated with IL-6 levels. Salivary cortisol was not associated with occupational pressure management.