Norovirus GII.4 genotype is a leading cause of nonbacterial gastroenteritis in infants. Effective vaccines against noroviruses are not yet available, enhancing the interest of the protection mechanisms elicited by breast milk that may contain norovirus-specific antibodies and histo-blood group antigens. The aims of our study were to analyze norovirus GII.4-specific antibodies in breast milk and serum and to assess their blocking activity on recombinant norovirus virus-like particles (VLPs) binding to saliva. Mature milk and serum from 108 mothers were analyzed for specific IgA to norovirus GII.4-2006b and for their blocking activity on the binding of norovirus GII.4-2006b VLPs to fucosyltransferase FUT2-positive and negative saliva. Norovirus GII.4-2006b-specific IgG antibodies were also analyzed in serum samples. Higher specific IgA titers were detected in mature milk (75%) than in serum samples (62%), showing a correlation between both results (ρ = 0.427, P = 0.000). However, only 56.3% of the serum samples contained norovirus-specific IgG. Almost all mature milk samples (99.1%) inhibited the binding of norovirus VLPs to FUT2-negative saliva; however, only 25% did so to FUT2-positive saliva (P = 0.000). Ninety percent of serum samples inhibited the binding of norovirus VLPs to FUT2-negative saliva. Breast milk inhibits norovirus GII.4-2006b VLPs binding to receptors in saliva, and anti-norovirus IgA antibodies are only partly responsible for this activity. The FUT2 status of the receptor seems to be a strong predictor of this effect, but more studies to ascertain the participation of histo-blood group antigens in the protection against norovirus infections elicited by breast milk are required.