Abstract Disease resilience is the ability of an animal to maintain performance under pathogen exposure but is difficult to select for because breeding populations are raised in biosecure, high-health facilities. Selection for resilience requires an indicator trait that is easy to measure on healthy young animals, heritable, and genetically correlated with resilience. Our objective was to investigate circulating Natural Antibody (NAb) levels as potential indicators for disease resilience in pigs. Data were from a natural polymicrobial disease challenge, in which batches of 60–75 weaned LWxLR barrows were sourced every three weeks (28 batches, 1799 pigs) from healthy multipliers. NAb and total IgG were evaluated by indirect ELISA in blood samples collected around 35 d of age. Disease resilience data were collected until pigs reached market age. All pigs were genotyped on a 650k panel. Genetic parameters were estimated by univariate and bivariate analyses in ASReml4. Single-marker and Bayesian variable selection methods were used for GWAS. Heritability estimates were lower for IgG NAb (0.03–0.22) than for IgM NAb (0.24–0.42) but maternal effects were larger for IgG (0.49–0.58) than for IgM (0.04–0.12). Phenotypically, IgM titers correlated with each other (0.26–0.71), as did IgG titers (0.40–0.81), but correlations between IgM and IgG were low (0.00–0.13). Genetic correlations showed similar patterns, ranging from 0.44–0.99, 0.45–0.84, and -0.30–0.25 for IgG, IgM, and IgG/IgM, respectively. Genetically, higher levels of NAb tended to be associated with fewer treatments, lower mortality, higher finishing ADG, and lower day-to-day fluctuations in feed intake but SE were large. Phenotypically, pigs that reached market age had significantly higher levels of IgG NAb than pigs that died. GWAS identified several genomic regions for NAb levels. In conclusion, levels of circulating NAb in healthy young piglets are potential indicators of polymicrobial disease resilience. Funded by Genome Canada and Alberta, and by USDA-NIFA.