Background The etiology of autism spectrum (ASD) and Attention Deficit/Hyperactivity (ADHD) disorders are multifactorial. Epidemiological studies have shown associations with environmental pollutants, such as plasticizers. This study focused on two of these compounds, the Bisphenol-A (BPA) and Diethylhexyl Phthalate (DEHP). The major pathway for BPA and DEHP excretion is via glucuronidation. Glucuronidation makes insoluble substances more water-soluble allowing for their subsequent elimination in urine. Hypothesis Detoxification of these two plasticizers is compromised in children with ASD and ADHD. Consequently, their tissues are more exposed to these two plasticizers. Methods We measured the efficiency of glucuronidation in three groups of children, ASD (n = 66), ADHD (n = 46) and healthy controls (CTR, n = 37). The children were recruited from the clinics of Rutgers-NJ Medical School. A urine specimen was collected from each child. Multiple mass spectrometric analyses including the complete metabolome were determined and used to derive values for the efficiency of glucuronidation for 12 varied glucuronidation pathways including those for BPA and MEHP. Results (1) Both fold differences and metabolome analyses showed that the three groups of children were metabolically different from each other. (2) Of the 12 pathways examined, only the BPA and DEHP pathways discriminated between the three groups. (3) Glucuronidation efficiencies for BPA were reduced by 11% for ASD (p = 0.020) and 17% for ADHD (p<0.001) compared to controls. DEHP showed similar, but not significant trends. Conclusion ASD and ADHD are clinically and metabolically different but share a reduction in the efficiency of detoxification for both BPA and DEHP with the reductions for BPA being statistically significant.