BACKGROUND: Prenatal alcohol exposure (PAE) impairs fetal growth and brain development. Dysregulated placental function contributes to these deficits. Whether PAE also disrupts its metabolic functions to impede fetal development is unclear. OBJECTIVES: We performed untargeted metabolomics to gain mechanistic insights on how PAE impacts placental metabolism and fetal nutrient availability. METHODS: Pregnant C57BL/6J mice were gavaged with alcohol (ALC, 3 g/kg) or isocaloric maltodextrin (CON) daily on embryonic days (E) E8.5 through E17.5. We performed untargeted metabolomics on placentas harvested at E17.5. RESULTS: Alcohol reduced placental glucose and glycolytic intermediates and increased tricarboxylic acid (TCA) cycle intermediates, suggesting a shift from glucose to lipids to meet its high energetic demands. This was complemented by elevations in intermediates of the pentose phosphate and glucosamine pathways, indicating a diversion of glucose into nonoxidative fates. Alcohol also decreased aspartate and asparagine, consistent with the limited glucose availability and increased fetal demand for nitrogen acceptors to support its increased gluconeogenesis and urea production. Alcohol also caused a selective increase in purine metabolites despite the limited availability of donor sources glucose, serine, glycine, glutamine, and asparagine. Uridine nucleotides were also elevated and may represent an adaptive change to meet the increased need for thiamin pyrophosphate in the oxidative decarboxylations of the TCA cycle and pentose phosphate pathways. Decreases in multiple oxylipins having antivasoconstriction actions could be a mechanism by which alcohol alters the placental vasculature and promotes vasoconstriction. Importantly, the selective and strong correlation of these dysregulated metabolites with reduced fetal brain weight, but not body weight, affirms the importance of the placenta-brain axis and placental metabolism on brain development. CONCLUSIONS: Alcohol causes metabolic dysregulation and reprogramming of the late-term placenta. These changes limit fetal nutrient availability and contribute to the reduced brain development and cognitive impairments that partly typify PAE.