Background The fusion (F) glycoprotein of respiratory syncytial virus (RSV) represents the major neutralizing antigen, and antibodies against the pre-F conformation have the most potent neutralizing activity. This study aimed to assess the correlation between maternal antibody titers against the pre-F, post-F, and G glycoproteins and the child's risk of developing severe RSV bronchiolitis early in infancy. Methods We identified previously healthy term infants <3 months of age hospitalized with RSV bronchiolitis from December 2015 to March 2016. We measured IgG antibody titers to pre-F, post-F, and G proteins in maternal sera obtained at 9-12 weeks of pregnancy of these hospitalized infants' mothers (n = 94) and compared them with serum antibody titers of control pregnant mothers (n = 130) whose children were not hospitalized. Results All maternal samples (n = 224) had detectable pre-F antibodies. Pre-F antibody titers were significantly lower in mothers whose infants were hospitalized with RSV bronchiolitis compared with those mothers whose infants were not hospitalized (23.9 [range (or antibody titer range), 1.4-273.7] mu g/L vs 30.6 [XXX, 3.4-220.0] mu g/L; P = .0026). There were no significant differences in maternal post-F and G antibody titers between hospitalized and nonhospitalized infants. Conclusions Our findings indicate that maternal pre-F antibodies are fundamental for providing immune protection to the infant. Maternal serum immunoglobulin antibody titers directed to respiratory syncytial virus (RSV) pre-F glycoprotein were lower in infants less than 3 months of age hospitalized with RSV bronchiolitis than in maternal serum samples of age-matched control infants who were not hospitalized.