This study evaluated the effect of (xeno)estrogenic mixtures on the metabolome of the Sydney rock oyster, Saccostrea glomerata through a one-week exposure in which a “low” and a “high” mixture of estrogens representing Australian and global relevant concentrations respectively were applied. The digestive gland, gill, and gonad tissues of both sexes were assessed for polar metabolites using proton (1H) Nuclear Magnetic Resonance (NMR) techniques. The soft body mass was reduced and major metabolites remarkably down regulated in the digestive gland due to both estrogenic exposures. However, a moderate effect was found in gills and female gonads with decreases in metabolites observed only after exposure to the high mixture. In contrast, the male gonad was unaffected by estrogen exposure. The major altered metabolites included carbohydrates, amino acids, intermediates of the tricarboxylic acid (TCA) cycle along with adenosine triphosphate (ATP). Thus, the overall findings demonstrate the impact of estrogenic mixtures on the metabolome at levels reported in receiving waters of Australia and globally. Impacts to carbohydrate metabolism and the TCA cycle translate to lower pools of available energy (i.e. ATP) which impacts the cellular homeostasis, somatic maintenance and growth, and the reproduction and fitness of oysters.