Captive breeding programs are often initiated to prevent species extinction until reintroduction into the wild can occur. However, the evolution of captive populations via inbreeding, drift, and selection can impair fitness, compromising reintroduction programs. To better understand the evolutionary response of species bred in captivity, we used nearly 5500 single nucleotide polymorphisms (SNPs) in populations of white-footed mice (Peromyscus leucopus) to measure the impact of breeding regimes on genomic diversity. We bred mice in captivity for 20 generations using two replicates of three protocols: random mating (RAN), selection for docile behaviors (DOC), and minimizing mean kinship (MK). The MK protocol most effectively retained genomic diversity and reduced the effects of selection. Additionally, genomic diversity was significantly related to fitness, as assessed with pedigrees and SNPs supported with genomic sequence data. Because captive-born individuals are often less fit in wild settings compared to wild-born individuals, captive-estimated fitness correlations likely underestimate the effects in wild populations. Therefore, minimizing inbreeding and selection in captive populations is critical to increasing the probability of releasing fit individuals into the wild.