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Background: Exposure to metals lead (Pb), mercury (Hg), and cadmium (Cd) and trace elements selenium (Se) and manganese (Mn) has been linked to the developmental origins of cardiometabolic diseases, but the mechanisms are not well-understood. Objective: Conduct a metabolome-wide association study to understand how in utero exposure to Pb, Hg, Cd, Se, and Mn affects the metabolic programming of fetuses. Methods: We used data from mother-infant pairs in the Boston Birth Cohort. We measured metals and trace elements in maternal red blood cells (RBCs) collected 24-72 hours after delivery, and metabolites in cord blood collected at birth. We used multivariable linear regression to examine associations of metals and trace elements with metabolites and Bonferroni correction to account for multiple comparisons. We assessed non-linear associations of metals and trace elements with metabolites using restricted cubic spline plots. Results: This analysis included 690 mother-infant pairs (57% Black and 24% Hispanic). After Bonferroni correction, 25 cord metabolites were associated with at least one metal or trace element (Figure). Pb was negatively associated with the xenobiotic piperine, Cd was positively associated with xenobiotics cotinine and hydroxycotinine, and Hg was associated with 8 lipid metabolites (in both directions). Mn and Se shared associations with 6 metabolites (in both directions), which mostly included nucleotides and amino acids; Mn was additionally associated C36:4 hydroxy phosphatidylcholine and Se was additionally associated with 7 metabolites (mostly amino acids, nucleotides, and carnitines). Most associations were linear. Discussion: Maternal RBC metal and trace element concentrations were associated in a dose-dependent fashion with cord blood metabolites. What remains to be determined is whether these metals- and trace elements-associated changes in cord metabolites can influence a child’s future risk of cardiometabolic diseases.