A major QTL for host response to porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) infection was identified in a previous study. Single nucleotide polymorphism WUR10000125 (WUR), which is in complete linkage disequilibrium with the putative causative mutation, can be used as a tag SNP for the QTL. However, the effect of WUR following PRRS vaccination and/or coinfection with other pathogens is not known. Therefore, objectives of this study were to estimate the effect of WUR on host response following PRRS vaccination and coinfection of PRRSV with porcine circovirus type 2b (PCV2b), to estimate genetic parameters for host response to vaccination and coinfection, and to estimate the effect of previously identified candidate SNP under PRRSV-only or PCV2b-only infection on host response to coinfection. Data from 2 trials, comprising a total of 396 commercial crossbred nursery pigs from a single genetic source, were used for all analyses. Pigs were preselected based on WUR genotype: approximately half AA and half AB, where B is the favorable and dominant allele. At weaning, pigs were shipped to Kansas State University, where half of the pigs were vaccinated with a PRRS modified live virus vaccine. Four weeks later, all pigs were coinfected with field strains of PRRSV and PCV2b and followed for 42 d. Body weight and serum viremia measurements were collected following vaccination and coinfection to calculate ADG and viral load (VL), respectively. Average heritability estimates for PRRS VL, PCV2b VL, and ADG were 0.29, 0.09, and 0.40, respectively. After vaccination, AB pigs had lower vaccination VL ( = 0.03) and faster gain ( = 0.004) than AA pigs, as expected. After coinfection, AB pigs had lower PRRSV VL ( < 0.001) but did not significantly differ from AA pigs in growth rate ( = 0.86). For PCV2b VL, suggestive evidence of an interaction between vaccination and WUR genotype ( = 0.11) was detected, where AB pigs had significantly lower PCV2b VL when vaccinated ( = 0.007) but not when they were not vaccinated ( = 0.87). In addition to WUR, several PRRS-associated SNP and a PCV2b-associated SNP had significant effects on host response to coinfection. In conclusion, marker-assisted selection based on WUR genotype alone, or along with other candidate SNP for PRRSV and PCV2b infection, is a promising strategy to select for improved host response to not just PRRS but also coinfection of PRRSV with PCV2b and perhaps other pathogens.