There are few early biomarkers to identify pregnancies at risk of preeclampsia (PE) and abnormal placental function. In this cross-sectional study, we utilized targeted ultra-performance liquid chromatography-electrospray ionization mass spectrometric (UPLC-ESI MS/MS) and a linear regression model to identify specific bioactive lipids that serve as early predictors of PE. Plasma samples were collected from 57 pregnant women prior to 24-wks of gestation with outcomes of either PE (n=26) or uncomplicated term pregnancies (n=31), and the profiles of eicosanoids and sphingolipids were evaluated. Significant differences were revealed in the eicosanoid, (±)11,12 DHET, as well as multiple classes of sphingolipids; ceramides, ceramide-1-phosphate, sphingomyelin, and monohexosylceramides; all of which were associated with the subsequent development of PE regardless of aspirin therapy. Profiles of these bioactive lipids were found to vary based on self-designated race. Additional analyses demonstrated that PE patients can be stratified based on the lipid profile as to PE with a preterm birth linked to significant differences in the levels of 12-HETE, 15-HETE, and Resolvin D1 (RvD1). Furthermore, subjects referred to a High-Risk OB/GYN clinic had higher levels of 20-HETE, arachidonic acid, and RvD1 versus subjects recruited from a routine, general OB/GYN clinic. Overall, this study shows that quantitative changes in plasma bioactive lipids detected by UPLC-ESI-MS/MS can serve as an early predictor of PE and stratify pregnant people for PE type and risk.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.