The objective of this study was to identify genomic regions associated with porcine reproductive and respiratory syndrome (PRRS) viral load (VL), porcine circovirus type-2b (PCV2b) VL, and weight gain (WG) in nursery pigs co-infected with PRRS virus (PRRSV) and PCV2b. Two PRRS Host Genetics Consortium trials were conducted using commercial crossbred pigs (n = 400) pre-selected (50% AA and 50% AB) for the WUR single nucleotide polymorphism (SNP) on chromosome (SSC) 4 that is associated with response to PRRS. Half of the pigs received a PRRS modified live vaccine and all pigs were co-infected with PRRSV and PCV2b 28 d later. For the genome-wide association studies (GWAS), 61,730 SNPs were fitted simultaneously using the BayesB method with π = 0.994. For analysis of PCV2b VL, trial, WUR, vaccination (Vx), WUR×Vx, weight at Vx, age at Vx, PRRS viremia at 0 dpi, PCV2b viremia at 0 dpi, and pen were fitted as fixed effects. For analysis of WG and PRRS VL, trial×Vx replaced WUR×Vx. Marker-based heritability estimates were 0.33, 0.34, and 0.14 for WG, PCV2b VL, and PRRS VL, respectively. Compared with AA pigs, AB pigs did not significantly differ (P = 0.70) in WG but had lower PRRS VL (P < 0.0001) and, in the vaccinated group, lower PCV2b VL (P = 0.09). Sizable genetic associations were identified for the GWAS of WG and PCV2b VL, but not for PRRS VL. A 2-Mb window on SSC9, at 27–28 Mb, explained 7.7% of genetic variance in WG, which has been associated with growth of nursery pigs across multiple breeds. For PCV2b VL, 1-Mb windows on SSC1 (162 Mb), SSC5 (102 Mb), and SSC7 (41 Mb) explained 1.4, 1.1, and 1.0% of genetic variance, respectively. Thus, the AB WUR genotype was associated with reduced PRRS VL and with reduced PCV2b VL in vaccinated pigs, following co-infection with PRRSV and PCV2b. Genomic regions associated with WG and PCV2b VL were identified, regions for the latter trait being novel. These results suggest the possibility of selectively breeding pigs, based on these regions, for improved host response to PRRSV/PCV2b co-infection. This work was supported by the USDA ARS NIFA awards 2012–38420–19286 and 2013–68004–20362.