Background Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs. It is characterized by production of autoantibodies and immune complex deposition in various organs, leading to inflammation and tissue destruction. Although the definite etiopathogenesis of SLE remains unclear, many different mechanisms may contribute to the pathogenesis of SLE. Galectin-3 is a member of beta-galactoside-binding lectins. It has an essential role in negatively regulating T-cell receptor. Aim The aim of this work was to estimate the plasma level of galectin-3-binding protein (G3BP) in patients with SLE to assess its possible role in pathogenesis of the disease and its correlation to disease activity. Patients and methods The current study included 25 patients with SLE and 25 healthy individuals who served as a control group. Patients were divided according to systemic lupus erythematosus disease activity index score. Peripheral venous blood samples were taken from each participant, and plasma was examined by enzyme-linked immunosorbent assay for quantitative evaluation of G3BP. Results G3BP was significantly increased in SLE compared with control group. There was a significant positive relation between plasma G3BP level and family history. No significant correlation was found between plasma G3BP level and duration of the disease. A significant positive correlation was found between G3BP and activity of the disease according to systemic lupus erythematosus disease activity index. Conclusion G3BP may play a role in the pathogenesis of SLE and may be useful for therapeutic intervention in patients with SLE.