BackgroundAdolescents and young adults (AYA) with a chronic somatic disease (CD) have a 3-fold higher risk of post-traumatic stress disorder (PTSD) than healthy controls. In addition, elevated post-traumatic stress symptoms (PTSS) have a negative impact on CD severity, treatment adherence, health problems and functional impairment. However, a more detailed understanding of this comorbidity is lacking.MethodsAYA with type 1 diabetes mellitus, juvenile idiopathic arthritis or cystic fibrosis (12–21 years of age) and elevated anxiety and/or depression symptoms, as well as their reference persons (≥ 18 years of age), completed online questionnaires in self- or observer report. The most stressful event related to the CD was reported descriptively. Questionnaires were used to assess PTSS, anxious and depressive symptoms, actual overall health, coping, personal growth and social support. Qualitative content analysis, linear regression models and correlations were used for mixed methods analysis.ResultsAccording to the reports ofn= 235 AYA (mean age 15.61; 73% girls) andn= 70 reference persons, four categories were identified as the most stressful events due to CD: (1) psychological burden (40% of AYA / 50% of reference persons); (2) CD self-management (32% / 43%); (3) social burden (30% / 27%); and (4) physical impairment (23% / 16%). 37% of AYA reported clinically relevant PTSS due to CD. The best predictors of PTSS severity were anxious-depressive symptoms, emotional coping, personal growth and current overall health (F(4, 224) = 59.404,R²= 0.515,p< .001). Of all categories, psychological (β= 0.216,p= .002) and social burden (β= 0.143,p= .031) showed significant association with the severity of PTSS (F(4, 230) = 4.489,R²= 0.072,p= .002). The more categories the most stressful event addressed, the higher was the PTSS symptom severity (r= .168,p= .010).ConclusionsMany AYA showed clinically relevant PTSS and reported experiencing stressful events in several areas of life through their CD. The association between the stressful event categories and other variables could help identify AYA with CD who need psychological interventions the most.Trial registration: German Clinical Trials Register (DRKS): DRKS00016714, registered on 25/03/2019 and DRKS00017161, registered on 17/09/201.