ObjectivesThis study aimed to assess the clinical complexity of patients with chronic systemic diseases (systemic lupus erythematosus [SLE] and ANCA-associated vasculitis [AAV]) using the INTERMED Self-Assessment questionnaire (IMSA) to determine the most important factors responsible for this phenomenon in these patients. MethodsThis was a cross-sectional, observational study. Questionnaires were used to evaluate biopsychosocial complexity (IMSA), quality of life (Short Form Survey [SF-36]), mental state (General Health Questionnaire – 28 [GHQ-28] and Hospital Anxiety and Depression Scale [HADS]), and acceptance of illness (Acceptance of Illness Scale [AIS]). ResultsThe final analysis included 81 patients. There was a moderate correlation between clinical complexity (total IMSA score) and quality of life related to mental health (SF-36) and mental state (GHQ-28) in patients with SLE. However, in patients with AAV, clinical complexity had a strong relationship with physical health-related quality of life and a moderate relationship with mental health-related quality of life. Stepwise regression analysis showed that low mental health-related quality of life is a predictor of higher complexity in SLE. The predictors of high clinical complexity in AAV were low physical and mental health-related quality of life and aggravated depressive symptoms (HADS). Other principal factors of clinical complexity were employment status, place of residence, social functioning, and illness duration. ConclusionThis study confirmed the importance of holistic attitudes and complex healthcare among patients with chronic diseases.