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Objective To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes. Methods Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records. Results A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑19PBDEs were detected in FGR cases than in controls. Increased BDE-207, -208, -209, and ∑19PBDEs levels in maternal serum were related to decreased placental length, breadth, surface area, birth weight, birth length, gestational age, and Quetelet index of newborns. After adjusting for confounders, BDE-207 and ∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR. Conclusion A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.