INTRODUCTION: Several epidemiological studies have reported that some organochlorine compounds (OCs), such as polychlorobiphenyls (PCBs) and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4'-DDE), may alter thyroid function. OBJECTIVE: The aim of the present study was to investigate the association of maternal serum OC concentrations of 4,4'-DDE and the sum of seven PCB congeners (PCB 28, 52, 101, 118, 138, 153, and 180) with thyroid hormone (TH) status. METHODS: We measured OC concentrations in 157 maternal serum samples at 12 weeks of pregnancy in a cohort from Valencia (Spain). Thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), and free thyroxine (FT4) were measured as biomarkers of thyroid function in the same samples. Linear and logistic regression analyses were performed between OCs and TH levels, and variables were log transformed. RESULTS: Mothers with higher levels of 4,4'-DDE had higher odds of having TSH levels >2.5 mIU/L (OR=2.53; 95% CI=1.36; 4.73; p=0.004), and we found a significant negative association between serum 4,4'-DDE concentrations and FT4 levels (beta=-0.03; 95% CI=-0.05; 0.00; p=0.050) after adjustment for covariates and total lipids. No association was found between sum of PCBs and TH levels. CONCLUSION: Serum concentrations of 4,4'-DDE were associated with increased TSH and reduced FT4 but not TT3 levels. Our results suggest that some environmental chemicals may interfere with the thyroid system of pregnant women. The major role that maternal THs may play in fetal neurodevelopment makes these findings especially relevant.