The complement (C') cascade is an important part of the innate immunity. It acts through three major pathways: classical (CP), alternative (AP) and mannose‐binding‐lectin (MP). C' reduction is a key feature in systemic lupus erythematosus (SLE), for its pathogenesis and for disease relapse. The aims of our study are to correlate C' variations with disease activity and verify the presence of C' deficiencies. We tested for three C' pathways 52 sera from 20 patients affected by SLE. A significant correlation between the ECLAM score and the degree of activation of the CP (Mann‐Whitney; P= 0.001) was recorded, while the correlation with anti‐dsDNA antibodies did not reach statistical significance (Mann‐Whitney; P > 0.05). In conclusion, the ELISA assay can be considered well suited for testing SLE samples. We detected a significant link between the phases of lupus activity and the reduction of the CP.