ABSTRACT.- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by severe joint inflammation, synovial hyperplasia and degradation of the cartilage and bone in the joint. Patients with RA have an amplified T helper (Th) 1 and Th17 immune response and production of autoantibodies by autoreactive B cells. In the joint, macrophages mediate bone destruction and maintain the inflammatory process in RA. There is an increasing body of evidence indicating that NADPH oxidase (NOX2)-rived reactive oxygen species (ROS), mainly produced by macrophages and neutrophils, may have effector functions in RA. In this work we characterized ROS production in both monocytes and macrophages in RA. Our results indicate that NOX2-dependent production of ROS attenuates inflammation and clinical signs by decreasing innate and adaptive immune responses in collagen-induced arthritis in mice. We also report that ROS production by circulating classical and non-classical monocytes from patients with RA negatively correlate with disease symptoms. Therefore, ROS produced by different monocyte subsets in peripheral blood might be considered as useful biomarkers or predictors of the immune response associated with RA disease activity. © 2025 European Federation of Immunological Societies. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.