Background: Fatty acids (FAs) are essential for fetal growth. Exposure to perfluorinated chemicals (PFCs) may disrupt FA homeostasis, but there are no epidemiological data regarding associations of PFCs and FA concentrations.

Objectives: We estimated associations between perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) concentrations and maternal levels of FAs and triglyceride (TG) and birth size of the offspring.

Methods: We analyzed 306 mother–child pairs in this birth cohort between 2002 and 2005 in Japan. The prenatal PFOS and PFOA levels were measured in maternal serum samples by liquid chromatography–tandem mass spectrometry. Maternal blood levels of nine FAs and TG were measured by gas chromatography–mass spectrometry and TG E-Test Wako kits, respectively. Information on infants’ birth size was obtained from participant medical records.

Results: The median PFOS and PFOA levels were 5.6 and 1.4 ng/mL, respectively. In the fully adjusted model, including maternal age, parity, annual household income, blood sampling period, alcohol consumption, and smoking during pregnancy, PFOS but not PFOA had a negative association with the levels of palmitic, palmitoleic, oleic, linoleic, α-linolenic, and arachidonic acids ( p < 0.005) and TG ( p- value = 0.016). Female infants weighed 186.6 g less with mothers whose PFOS levels were in the fourth quartile compared with the first quartile (95% CI: –363.4, –9.8). We observed no significant association between maternal levels of PFOS and birth weight of male infants.

Conclusions: Our data suggest an inverse association between PFOS exposure and polyunsaturated FA levels in pregnant women. We also found a negative association between maternal PFOS levels and female birth weight.