Objective The aim of this study was to examine if maternal plasma concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-2 change prior to the diagnosis of preeclampsia. Study Design A longitudinal study was conducted in normal pregnant women (n = 160) and patients with preeclampsia (n = 40). Blood samples were collected at 7 gestational age intervals from 6 weeks to term. Plasma concentrations of sVEGFR-2 were determined by enzyme-linked immunosorbent assay. Analysis was performed with cross-sectional and longitudinal (mixed effects model) approaches. Results Mothers destined to develop preeclampsia have lower plasma sVEGFR-2 concentrations than those who will have a normal pregnancy (longitudinal approach; P < .05). Cross-sectional analysis suggested that the median plasma sVEGFR-2 concentration in women destined to develop preeclampsia was significantly lower than that in normal pregnant women from 28-31 weeks of gestation ( P = .001) or 6-10 weeks prior to the diagnosis ( P < .001). Conclusion A lower maternal plasma sVEGFR-2 concentration precedes the development of preeclampsia, both term and preterm.