Colostrum with sufficient antibodies is essential for the newborn calf, as it requires this passive immunity to survive until weaning. High variation in the amount of colostrum antibodies in Swedish dairy cows has been reported, with a large proportion having low antibody levels. Natural antibodies (NAb) are produced without any antigenic stimulation and target self-antigens and pathogen-associated molecular patterns (PAMPs). Our objective was to estimate genetic parameters and detect quantitative trait loci (QTL) for 2 NAb isotypes (IgG, IgM) in colostrum binding keyhole limpet hemocyanin (KLH) and muramyl dipeptide (MDP). Three experimental farms were included in the study, 1719 colostrum samples from 1313 cows between 1 to 6 parities, calving from January 2015 to April 2017 were collected. 70% of the animals were Swedish Red and 30% Swedish Holstein. Antibodies were measured from colostrum using indirect ELISAs. To estimate genetic parameters, a linear mixed model with repeated measures (different calvings from the same cow) was run using ASReml 4, correcting for cow parity number, time from calving to colostrum sampling and breed, including herd-year-season of calving and sample storage plate as random effects. An imputed 50K SNP array from a LD 7K array was used for the Genome-wide association study (GWAS), running the same model but including the SNP genotype as a fixed effect. Heritabilities for colostrum NAbs ranged from 0.15 to 0.27, with a permanent environment effect for IgG isotypes accounting for 30% of the variance and for IgM ranging from 15 to 19%. Genetic correlations between IgG and IgM ranged from 0.1 to 0.4. The GWAS revealed one QTL on BTA3 for IgM (KLH and MDP), the latter comprised of 7 SNPs (−log₁₀(P) = 4.4), 2 significant and 5 suggestive, ranging from 80 to 105 Mbp and another QTL on BTA7 for IgG (KLH and MDP) consisting of 3 SNPs (−log₁₀(P) = 4.1), from 85 to 113 Mbp. Our results suggest that natural antibodies can potentially provide an effective tool to improve colostrum quality using genetic selection.