Autoantibodies specific for double stranded DNA (anti-dsDNA Abs) are a serological biomarker of systemic lupus erythematosus (SLE) and constitute useful tools for monitoring many SLE patients. A new automated immunofluorescence and quantitative assay (EliA dsDNA) has recently become available. Its performance has been demonstrated to be equivalent to the Farr and Crithidia luciliae fluorescence (CLIFT) tests. The aim of the present work was to assess the utility of this new assay to monitor clinical activity in a large cohort of SLE patients. To this end, 1020 sera from 181 SLE patients were evaluated by the two methods. Results showed a higher frequency of positive results of anti-dsDNA Abs during lupus flares measured by EliA dsDNA than by CLIFT. Likewise, titers of those Abs were significantly increased in active SLE in comparison with inactive SLE when measured by EliA dsDNA but not by CLIFT. Serum titers of anti-dsDNA Abs by both assays showed a significant negative association with concentrations of C3 and C4. In summary, this retrospective study on a large cohort of patients demonstrated that EliA dsDNA was at least as useful as CLIFT as monitoring tool in the follow-up of SLE patients, but with the advantages of being automated, quick and quantitative.