Patients with inflammatory bowel disease (IBD) often experience severe impairment in different life domains. Psychological factors, such as illness perceptions and coping, may play a role in the adjustment to IBD as indicated by mental and physical health, activity, and work impairment. The present study aimed at examining the assumption of the Common Sense Model (CSM) that coping mediates the relationship between illness perceptions and adjustment in patients with IBD. In a cross-sectional design, 211 IBD patients (73 % Crohn's disease, 40 % male, mean age 42.9 +/- 12.9 years) attending an outpatient clinic completed questionnaires assessing illness perceptions (IPQ-R), coping (CORS), mental and physical health (SF-36), as well as activity and work impairment (WPAI). Multiple mediation analyses were applied that allow estimating the total and direct effects of all illness perception dimensions and the indirect effects through all coping strategies on the illness outcomes simultaneously. The analyses yielded significant direct effects of perceptions regarding the cyclical course, the chronic course, the severity of the consequences, the comprehensibility, and the emotional impact of IBD on study outcomes. Additionally, significant indirect effects were found for the perceptions regarding the severity of the consequences, the possibility of personal control, and the comprehensibility of IBD on mental and physical health as well as activity impairment through the use of one specific coping strategy, i.e., reduction of activity. The results provide evidence for the assumptions of the CSM and suggest the importance of addressing illness perceptions and activity stimulation in quality health care for IBD patients.