Prenatal maternal diet may influence disease susceptibility in offspring with specific genetic backgrounds. We hypothesized that interactions between prenatal antioxidant intake and polymorphisms in immunity genes influence respiratory tract infection (RTI) susceptibility in infants at 12 months of age. This study included 550 infants. In the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort study, prenatal maternal diet was assessed by administering a food frequency questionnaire. Infants' cord blood was genotyped for CD14 (rs2569190), TLR4 (rs1927911), and GSDMB (rs4794820) polymorphisms by the TaqMan method. Higher prenatal intake of total fruit and vegetables (FV) was associated with the decreased risk of RTI in offspring (P-trend=0.0430). In children with TT genotype at rs2569190, a higher prenatal intake of vitamins A and C, fruits, and total FV decreased RTI risk (P-trend < 0.05), while in infants with TC+CC genotype, a higher prenatal intake of fruit increased RTI risk (P-trend < 0.05). When analyzing the 3 genotypes, children with TT genotype at rs2569190 were more protected against RTIs compared with those with CC genotype with respect to vitamin C and fruits [odds ratio (OR)=5.04 and OR=10.30, respectively]. In children with CC genotype at rs1927911, RTI risk showed a dose-response association with a higher prenatal intake of vitamin C (P for interaction < 0.05). A higher prenatal intake of fruits and total FV reduced RTI risk in infants with GA+AA genotype of rs4794820 (P for interaction < 0.05). Prenatal antioxidant intake may reduce RTI risk in infants and this relationship may be modified by CD14, TLR4, and GSDMB polymorphisms.