Preeclampsia has been shown to be associated with changes in cerebral structure and cognitive function later in life. Nf (neurofilaments) are specific scaffolding proteins of neurons, and their quantification in serum has been proposed as a biomarker for neuroaxonal injury. We performed a prospective, longitudinal, single-center study at the University Hospital of Basel to determine serum Nf concentrations in pregnant women with singleton pregnancies and with high risk of preeclampsia or with early signs of preeclampsia. Enrollment started at 21 weeks of gestation, followed up with multiple visits until delivery. Sixty out of 197 women developed preeclampsia (30.5%). NfL (Nf light chain) was measured with a highly sensitive single molecule array (Simoa) assay, in addition to the established preeclampsia markers sFlt-1 (soluble fms-like tyrosine kinase-1) and PlGF (placental growth factor). The most important independent predictors of NfL were maternal age, number of pregnancies, and proteinuria. NfL levels increased during pregnancy and were significantly higher in women developing preeclampsia. The discriminatory accuracy of NfL, PlGF, and sFlt-1 in receiver operating characteristic curves analysis (area under the curve) of the overall group was 0.68, 0.81, and 0.84, respectively, and in women older than 36 years 0.7, 0.62, and 0.79, respectively. We conclude that increased axonal injury serum marker NfL predicts preeclampsia particularly in older women, with an accuracy similar to the established angiogenic factors. NfL may serve as an early indicator of preeclampsia-induced changes in cerebral structure and may help to stratify disease management.