The discovery of novel biomarkers for metabolic disease can refine nutritional interventions aimed at improving dairy cow health and performance. Therefore, our objective was to identify metabolites associated with common markers of metabolic disease. Thirty multiparous Holstein cows were enrolled −28 d prepartum and fed diets formulated to meet or exceed requirements. Blood and liver samples were routinely collected from enrollment through d 14 postpartum (pp). To characterize the plasma lipidome spanning 9 time points, untargeted lipidomics was performed using quadrupole time-of-flight mass spectrometry. Univariate and multivariate analyses of normalized, auto-scaled lipidomic data were performed. Based on pp metabolic health data, cows were separately categorized into low or high free fatty acid area under the curve (FFA_AUC; d 1 – 14 pp; 4,915 ± 1,369 vs. 12,501 ± 2,761 [μmol/L × 14 d]; n = 18), β-hydroxybutyrate area under the curve (BHB_AUC; d 1 – 14 pp; 4,583 ± 459 vs. 7901 ± 1,206 [μmol/L × 14 d]; n = 18), or mean pp liver lipid content (d 5 and 14 pp; 5 ± 1 vs. 12 ± 2% of wet weight; n = 18). Significant variables associated with a specific category were identified based on leverage/squared prediction error plots. Lipidomics revealed 301 plasma lipids including 8 cholesterol esters, 163 phospholipids, and 130 acylglycerols. Independent of category, all cows displayed dramatic decreases in plasma triacylglycerols and monoalkyl-diacylglycerols (P < 0.01), and the majority of phospholipids reached a nadir at parturition (P < 0.01). Analyses revealed that phosphatidylcholine (PC) 32:3, 35:5, 37:5 were specific for high FFA_AUC, PC 31:3, 32:3, 35:5, and 37:5 were specific for high BHB_AUC, and PC 31:2, 31:3, and 32:3 were specific for high liver lipid. Notably, PC 32:3 was specific for high FFA_AUC, BHB_AUC, and liver lipid cows, a metabolite that was lower in abundance relative to the low categories (P < 0.01). Other lipids specific for 2 or more categories included phosphatidylglycerol 38:4 and lysophosphatidylcholine 15:0. Nutritional interventions that increase plasma PC 32:3 during the peripartum should be explored.