Objective: Circulating biomarkers of endothelial dysfunction and inflammation are elevated in late pregnancy in women with preeclampsia. We examined plasma levels of inflammatory cytokines and adhesion molecules in early pregnancy, to assess their ability to predict preeclampsia. <p/>Methods: In a prospective longitudinal study, 2600 women with singleton pregnancies and no history of hypertension were recruited at their antenatal hospital (booking) visit at gestational week 12–16. Of these, 49 (1.9%) developed preeclampsia, whereas 74 women matched for age and BMI with uncomplicated pregnancies were selected as controls. A subset of women with risk factors for preeclampsia were sampled again at gestational weeks 16 and 28 (11 cases, 39 controls) and postnatally (six cases, 36 controls). <p/>Results: From multiplex analysis, soluble E-selectin concentrations were higher at 12–16 weeks in women who subsequently developed preeclampsia (15.1 ± 4.9 versus 12.9 ± 4.5 ng/ml, P = 0.02). At gestational week 28, E-selectin concentrations were again higher in women who went on to develop preeclampsia compared with controls (14.4 ± 5.6 versus 10.7 ± 3.5 ng/ml, P = 0.010), whereas levels were not different between the two groups in postpartum samples. <p/>Conclusion: Changes in soluble E-selectin concentration in early pregnancy may reflect underlying pathophysiological processes, potentially providing mechanistic insights into preeclampsia.