Serum antibodies to bovine norovirus have been found recently in about 22% of humans. Whether this prevalence reflects limited virulence properties of the virus or that inherited host factors provide protection against bovine norovirus infection in humans remains to be established. To investigate whether histo-blood group antigens correlate with the presence of bovine norovirus (GIII.2) antibody, plasma (n = 105) from Swedish blood donors, genotyped and phenotyped for secretor, Lewis and ABO, were tested and compared for the frequency of IgG antibody and antibody titer to Bo/Newbury2/76/UK. In total, 26.7% (28/105) of Swedish blood donors were antibody-positive. Two non-secretors (2/21, 9.5%) were antibody-positive compared with 26/84 (31%) secretors (P = 0.047). While no statistically significant correlation was found between the frequency of antibodies to bovine norovirus and different ABO blood groups, individuals with blood type B presented the highest frequency of antibodies (37.5%) compared with 0–30% among other blood groups. Individuals with Le(a−b+) had not only higher frequency of antibodies (31.3%) compared with Le(a+b−) (11%) (P = 0.068) but also higher antibody titer (P = 0.085) although this was not significant statistically. No detectable cross-reaction between bovine GIII.2 and human GII.3 NoV VLP was found with human and animal sera. The results of this study suggest that bovine norovirus infections occur in Sweden and that secretor status but not ABO blood groups is a possible risk factor for infection. J. Med. Virol. 82: 1241–1246, 2010. © 2010 Wiley-Liss, Inc.