Prenatal exposure to vanadium has been associated with reduced birth size, however, the specific molecular mechanism underlying this effect remains largely unexplored. We measured vanadium in maternal plasma during early pregnancy, and characterized metabolomics profiling in cord blood among 1020 mother-infant pairs from the Wuhan Healthy Baby Cohort, China. After adjusting for potential confounders, a 2-fold increase in maternal plasma vanadium concentration was associated with a decrease of 25.1 g (95 % CI: -45.1, -5.1) and 0.429 g/cm (95 % CI -0.758 to -0.101) in birth weight and weight-for-length (WFL), respectively. Of the 423 metabolites detected, 42 metabolites and 10 metabolic pathways were significantly linked to both vanadium and birth size. The effect of vanadium on reduced birth weight and WFL was significantly mediated by 14 metabolites, including 2 hormones (cortisol and corticosterone), 1 amino acid (lysine), and 11 lipids, with a mediating effect range of 7 % to 17 %. In addition, the lysine degradation pathway significantly mediated a 19 % change in the association between vanadium exposure and both lower birth weight and WFL. Higher maternal vanadium exposure was linked to reduced birth size, and the perturbed metabolites and pathways involved in hormones, amino acids, oxidative stress, and lipid peroxidation may explain the mechanism.