In a previous study, the ability of gas chromatography time-of-flight mass spectrometry to detect potential metabolic biomarkers in preeclampsia was demonstrated. In this study, the authors sought to validate their preliminary findings in an entirely different patient cohort using a complementary, novel, and powerful combination of analytical tools (ultra performance liquid chromatography and LTQ Orbitrap mass spectrometry system). Eight metabolites that appeared in the authors' previous patient cohort were identified as being statistically significant (P < .01) as discriminatory biomarkers. The chemical identities of these 8 metabolites were established using authentic chemical standards. They included uric acid, 2-oxoglutarate, glutamate, and alanine. This is the first study to identify, in an unbiased manner, a series of small-molecular-weight metabolites that effectively detect preeclampsia in plasma. The identity of these metabolites provides new insights into the pathology of this condition and raises the possibility of the development of a predictive test.