- Background and aims Threatening life experiences and adverse family relations are major psychosocial stressors affecting mental and physical health in chronic illnesses, but their influence in Crohn’s disease (CD) is unclear. We assessed whether these stressors would predict the psychological and medical condition of CD patients. Methods Consecutive adult CD patients completed a series of instruments including demography, Patient Harvey–Bradshaw Index (P-HBI), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), short-form survey instrument (SF-36), brief symptom inventory (BSI), family assessment device (FAD), and list of threatening life experiences (LTE). Associations of FAD and LTE with P-HBI, SIBDQ, SF-36, and BSI were examined by multiple linear and quantile regression analyses. Results The cohort included 391 patients, mean age 38.38±13.95 years, 59.6% women, with intermediate economic status. The median scores were as follows: P-HBI 4 (2–8), FAD 1.67 (1.3–2.1), LTE 1 (0–3), SF-36 physical health 43.75 (33.7–51.0), SF-36 mental health 42.99 (34.1–51.9), and BSI-Global Severity Index 0.81 (0.4–1.4). The SIBDQ was 47.27±13.9. LTE was associated with increased P-HBI in all quantiles and FAD in the 50% quantile. FAD and LTE were associated with reduced SIBDQ (P<0.001). Higher LTE was associated with lower SF-36 physical and mental health (P<0.001); FAD was associated with reduced mental health (P<0.001). FAD and LTE were associated positively with GSI in all quantiles; age was associated negatively. Conclusion CD patients with more threatening life experiences and adverse family relations were less healthy both physically and mentally. Physicians offering patients sociopsychological therapy should relate to threatening life experiences and family relations.