The current distribution of the bighorn sheep in Mexico represents a reduced proportion of its original area. Previous population genetics studies conducted in Mexico have only included data from Tiburon Island in the Gulf of California and few individuals from the continent. The aim of this article was to describe aspects of the population genetics of Mexican bighorn sheep in order to aid in the management and conservation of the species. We analyzed 117 samples from the states of Sonora and Baja California Sur using 91 intersimple sequence repeat loci. Our results indicated that the Mexican samples of bighorn sheep have relatively low levels of genetic diversity (H ≈ 0.26) and low genetic differentiation (ϴ ≈ 0.07) that may be the result of the recent colonization and origin of the populations in Mexico. The individuals from Southern Baja California are genetically different from the Sonoran sample, but this genetic differentiation is low, perhaps due to the low levels of genetic variation of the Mexican populations. The results obtained in this study are relevant for population management of the bighorn sheep in Mexico in order to design translocation plans and management strategies to maintain genetic diversity and, in consequence, the health and future survival of the populations.