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<jats:sec><jats:label /><jats:p>Eur J Clin Invest 2011; 41 (6): 579–583</jats:p></jats:sec><jats:sec><jats:title>Abstract</jats:title><jats:p><jats:bold>Background </jats:bold> Over the years, the demonstration and confirmation of cell‐free DNA in the circulation has increasingly been recognized as a valuable diagnostic tool. Likewise, it has been known for some time that DNA structures that are targeted by auto‐antibodies play a central role in systemic lupus erythematosis (SLE) and that DNA‐antibody complexes in the circulation are one of the hallmarks of SLE. Investigating whether and to what degree fluctuations in free plasma DNA levels in patients with SLE might correspond to disease severity was therefore the goal of this investigation.</jats:p><jats:p><jats:bold>Methods </jats:bold> Blood from 13 patients with SLE and from 13 healthy controls was taken and analysed for the presence of anti‐dsDNA, anti‐ssDNA, anti‐nucleosome, anti‐histone antibodies as well as for cell‐free DNA concentrations. For each patient, the SLE disease activity index (SLEDAI) was calculated.</jats:p><jats:p><jats:bold>Results </jats:bold> As demonstrated herein, compared to healthy subjects, cell‐free DNA plasma levels in patients with SLE were significantly increased and so were anti‐dsDNA, anti‐ssDNA, anti‐histone and anti‐nucleosome antibodies. Furthermore, a statistically significant correlation was noted between cell‐free DNA and anti‐histone antibodies in patients with SLE. However, no correlation was noted between disease activity and anti‐dsDNA, anti‐ssDNA and anti‐nucleosome antibody concentrations. Surprisingly, and more important in the context of this study, there was no correlation between cell‐free DNA levels and SLEDAI scores.</jats:p><jats:p><jats:bold>Conclusions </jats:bold> The presented data seem to exclude measuring free plasma DNA as an inexpensive, simple and quick tool to assess disease activity in patients with SLE. Further studies on a larger patient population would be needed to confirm our results.</jats:p></jats:sec>