Objectives Circulating cell-free DNA (cfDNA) may result from cell damage and DNA fragments release, and, therefore, might be increased in inflammatory conditions. Preeclampsia (PE), an important cause of maternal and fetal mortality, is an inflammatory and oxidative condition. Our aim was to quantify cfDNA in Portuguese preeclamptic pregnancies, in order to search for a relationship with inflammation, endothelial dysfunction and severity of the disease. Methods Maternal blood was collected from 31 normal pregnant women and from 33 PE pregnant women in the 3rd trimester. Circulating cfDNA was measured in serum samples using a rapid direct fluorescent assay (Goldshtein et al. Ann Clin Biochem 2009;46:488–94), which does not require prior processing of samples, there is no need for DNA extraction and amplification, is accurate, sensitive, and reproducible. TNF-alpha, a pro-inflammatory cytokine and endothelial markers, tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1) antigen and soluble vascular cell adhesion molecule (sVCAM) levels, were evaluated by enzyme-immunoassay. Results Cf-DNA, TNF- α , sVCAM, tPA and PAI-1 concentrations were significantly higher in PE pregnant women when compared with normotensive pregnant women. In PE pregnancy cfDNA was significantly and positively correlated with TNF-alpha, VCAM, tPA and PAI-1 levels. CfDNA levels were also positively correlated with the PE severity, estimated by proteinuria. Conclusions Our data suggest that the associated inflammation and endothelial dysfunction in PE pregnancy seems to lead to an increase in cfDNA, and its levels seem to be a potential marker of PE severity. Thus, cfDNA might be a potential candidate in the noninvasive diagnostic field. Moreover, further studies are warranted to evaluate cfDNA value as a premature marker to the development of PE. Disclosures C. Catarino: None. S. Coimbra: None.L. Belo:None. S. Rocha: None. M. Bicho: None. I. Rebelo: None. A. Santos-Silva: None.