Variation at Major Histocompatibility Complex (MHC) genes is thought to be an important mechanism underlying mate choice in vertebrates, with individuals typically predicted to prefer MHC-dissimilar reproductive partners. However, analyses based on individual MHC loci have generated contradictory results regarding the role of these genes in mate choice decisions. To provide a more comprehensive assessment of relationships between MHC variation and mating behavior, we used an exome capture strategy to characterize variability at 13 MHC loci, 312 innate immune system genes, and 1,044 non-immune genes in 25 obligate monogamous pairs of California mice (Peromyscus californicus) from two free-living populations of this species in Monterey County, California. Pairwise genotypic comparisons and analyses of SNP-based allelic differences failed to detect disassortative mating based on MHC variability; reproductive partners were not more dissimilar than randomly generated male-female pairs at MHC, innate or non-immune loci. Within populations, individuals tended to be more closely related at MHC genes than at innate or non-immune genes. Consistent with the functional role of immunogenes, the two study populations were highly differentiated at MHC and innate genes but not at non-immune loci. Collectively, our results suggest that MHC genetic variation in California mice reflects local differences in pathogen exposure rather than disassortative mating based on variability at MHC Class I and II genes.