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Context: Studies suggest many essential trace metal(loid)s are involved in glucose metabolism, but the associations among pregnant women are unclear., Objective: To assess associations between early pregnancy plasma zinc, selenium, copper, and molybdenum levels and blood glucose levels later in the second trimester., Design: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies‒Singleton Cohort is a prospective cohort study conducted between July 2009 and January 2013., Setting: Twelve academic research hospitals in the United States., Patients: A total of 1857 multiracial, nonobese, healthy women., Main Outcome Measure: Blood glucose levels from 1-hour 50-g gestational load test (GLT) at 24 to 28 weeks of gestation., Results: Higher concentrations of first-trimester copper were associated with higher glucose levels from the GLT (i.e., every 50% increase in copper concentration was related to 4.9 mg/dL higher glucose level; 95% CI: 2.2, 7.5 mg/dL) adjusted for maternal sociodemographic characteristics and reproductive history. In contrast, every 50% increase in molybdenum concentration was associated with 1.2 mg/dL lower mean glucose level (95% CI: -2.3, -0.1 mg/dL). The magnitude of these associations was greater at the upper tails of glucose level distribution based on quantile regressions of the 10th, 50th, and 90th percentiles., Conclusions: Higher copper and lower molybdenum concentrations could increase the risk of glucose dysregulation during pregnancy, with women at higher risk of gestational diabetes mellitus potentially affected to a greater extent. Further work is needed to understand the mechanisms involved with early pregnancy essential metal(loid)s to inform clinical diagnosis and prevention of glucose intolerance during pregnancy., (Copyright © 2019 Endocrine Society.)