Inflammatory bowel disease (IBD) is group of chronic diseases that cause symptoms such as abdominal pain, urgent diarrhoea and fatigue, as well as associated complications (e.g., arthritis). Literature has pointed that IBD may cause depressive symptomatology, which seems to aggravate physical symptoms in a cycle of depression and inflammation. This study's aims to examine the mediator roles of chronic illness-related shame and experiential avoidance in the relationship between IBD symptomatology and depression, while controlling for associated medical complications. The sample comprised 161 adult IBD patients (52 males and 109 females), with a mean age of 36.73 (SD = 10.93), that completed validated measures. The hypothesised model was tested through path analyses. Results (see Fig. 1) showed that although IBD symptomatology presented a direct effect of .13 on depression, the majority of its impact was mediated through chronic illness-related shame and experiential avoidance with an indirect effect of 0.22. Indeed, IBD symptomatology seemed to lead to higher chronic illness-related shame, which presented a direct effect on depression of .15 and an indirect effect mediated by experiential avoidance of 0.37. This model presented excellent goodness-of-fit indices. These findings suggest that targeting shame and experiential avoidance in IBD patients would have beneficial outcomes for patients’ well-being. It thus seems that compassion and acceptance-based psychotherapies should be included in treatment programs for IBD.