Objective To detect the levels of cell-bound complement activation product (C4d) and immunoglobulins (IgG and IgM) on T and B lymphocytes in patients with systemic lupus erythematosus (SLE), and to evaluate the relationships between C4d and immunoglobulins (Ig) on lymphocytes, and finally to evaluate their diagnostic value for SLE. Methods A cross-sectional study including 142 SLE patients, 144 patients with other non-SLE autoimmune diseases and 100 healthy individuals was conducted. C4d and immunoglobulins on peripheral T and B lymphocytes (T-C4d, B-C4d, T-Ig and B-Ig) were measured by flow cytometry. In vitro immunobinding experiment was performed to characterize serum Ig from SLE patients to generate T-C4d, B-C4d, T-Ig and B-Ig. ANA, anti-dsDNA, anti-Smith antibody and other biomarkers were measured. Area under the receiver operating characteristic curve (AUC), nonparametric tests, partial correlation analysis, sensitivity and specificity were used for statistical analysis. Results Levels of T-C4d, B-C4d, T-Ig and B-Ig were found to be highest in SLE patients. Levels of T-C4d, B-C4d, T-Ig and B-Ig in non-SLE patients were also significantly higher than those in healthy individuals. T-C4d was positively correlated with T-Ig (r=0.587), as well as B-C4d vs B-Ig (r=0.734). Purified Ig from SLE plasma generated higher levels of T-C4d, B-C4d, T-Ig and B-Ig than Ig-removed SLE plasma. AUC of T-C4d, B-C4d, T-Ig and B-Ig were 0.733, 0.834, 0.707 and 0.825, respectively. Compared with anti-dsDNA antibody (38.7%), the sensitivity for SLE diagnosis increased significantly when the combination of T-C4d, B-C4d, T-Ig and B-Ig (85.2%) was made. Conclusion The autoantibody is a key factor for cell-bound C4d formation, and T-C4d, B-C4d, T-Ig and B-Ig may be reliable indicators for the diagnosis of SLE.