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Objectives The objective of this study is to determine: (1) if circulating copeptin, a stable biomarker of vasopressin secretion, is higher throughout gestation in pregnant women who develop preeclampsia in comparison to controls, and (2) if copeptin predicts the development of preeclampsia. Methods In this case-control study, coded plasma from mothers who developed preeclampsia ( n  = 50, PE), pregnant controls ( n  = 54, PC), and nonpregnant controls ( n  = 33, NC) with their annotated clinical patient information were obtained through the University of Iowa IRB-approved Women’s Health Tissue Repository. Copeptin, cystatin C (measure of renal function), LNPEP (vasopressinase), and sFLT-1 were measured using commercial ELISA kits. Multivariate regression models and receiver operating characteristics curves were constructed. Alpha was set at 0.05. Results In the first (654 ± 78 vs. 1852 ± 363 pg/mL, p p  = 0.01), and third (807 ± 158 vs. 1782 ± 263 pg/mL, p  = 0.002) trimesters, the PE group exhibited a significantly higher copeptin concentration in comparison to the PC and NC groups. There was no difference in copeptin between the PC and NC groups. Overall, there were no significant differences in Cystatin-C, LNPEP, and sFLT-1 between the PE and PC groups. Copeptin significantly predicts preeclampsia throughout gestation as early as the 6th week of gestation in the first trimester (AUC = 0.90, p Conclusions Copeptin is a novel, robust and clinically useful biomarker for the prediction of preeclampsia in very-early pregnancy. Disclosures: M. Santillan holds 2 provisional patents on the use of the vasopressin pathway in the prediction, prevention, and treatment of preeclampsia. D. Santillan: None. S. Scroggins: None. J. Min: None. K. Leslie: None. S. Hunter: None. G. Zamba: None. K. Gibson-Corley: None. J. Grobe: holds 2 provisional patents on the use of the vasopressin pathway on the prediction, prevention and treatment of preeclampsia.