Objective. To analyze specific characteristics and mechanisms underlying the development of organ pathology in patients with chronic brucellosis (CB). Patients and methods. This study included more than 500 patients with CB treated in Saratov hospitals in 2003–2018. In addition to standard examination, all study participants have undergone the assessment of their lipid peroxidation/antioxidant defense system, levels of major cytokines, markers of endotoxicosis (ET), and tissue-specific autoreactive antibodies. Results and discussion. The vast majority of patients (98.2%) had their musculoskeletal system affected; lesions to the autonomic nervous system and peripheral nervous system were observed in 97.5% and 88.8% of patients, respectively; almost half of males (45%) had their reproductive organs affected; approximately one-third of participants (26.7–32.9%) had cardiovascular disorders with myocardial lesions. The severity of systemic inflammation, ET, and autoimmune reactions depended on the CB activity and determined the development of organ pathology. We found that vascular and mechanical factors were important for the development of lesions to the peripheral nervous system and reproductive organs in men. Patients, in whom the diagnosis of CB was verified 2 years following onset of symptoms, were more likely to develop exacerbations, had more organs and systems affected, and had higher risk of disability. Conclusion. Comprehensive examination revealed multiple organ lesions in all CB patients, associated not only with damage caused by the pathogen at the site of specific inflammation, but also with the involvement of vascular and mechanical factors, as well as the consequences of systemic inflammatory response, ET, and autoimmune reactions. Late diagnosis was associated with more severe clinical manifestations of CB. © 2021, Dynasty Publishing House. All rights reserved.