The aim of this study was to determine the association between maternal oxidative stress and adverse birth outcome, and serum vitamin levels and paraoxonase (PON) polymorphism during pregnancy. We investigated 276 pregnant women who visited a hospital for prenatal care during gestational weeks 24 and 28. We measured serum Vitamins C and E levels and urinary levels of 8-hydroxy-2-deoxyguanosine (8-OH-dG). We determined the presence of a maternal PON polymorphism (Q-to-R substitution at a nucleotide located on 7q21.3) using a polymerase chain reaction-restriction fragment length polymorphism assay. High levels (relative to the median) of Vitamins C and E were associated with a reduced concentration of urinary 8-OH-dG, but increased birthweight and gestational age in subjects with the Q/Q and Q/R types of PON polymorphism. Even with the high-risk PON polymorphism (R/R), the results show that birthweight increased with high levels of Vitamins C and E. Our data demonstrate that oxidative stress and neonatal birthweight are affected by maternal levels of Vitamins C and E in subjects with a PON polymorphism.