Gene duplication is considered an essential mechanism of adaptive molecular evolution. One labile region of many gnathostome genomes that undergoes changes via duplication is a cluster comprised of hemoglobin (hb) family members. Gnathostome globin genes originated from a single proto-hb gene and duplicated individually, or in multiples, to generate expanded hb repertoires. Thus, genomic intervals of hb genes provide the opportunity to evaluate gene diversification in the context of selective environmental pressures. Hb clusters, however, diversify through both gene duplication and loss. Important examples of gene loss have been shown to be preceded by environmental change. Therefore, to determine how an environmental shift can impact a hb repertoire, we evaluated the genomic structure of a hb cluster in Astyanax mexicanus, a species supporting two morphotypes: a surface- and a cave-dwelling form. Prior studies indicated reduced oxygen levels in the caves of the Sierra de El Abra, suggesting that cave-dwelling forms have adapted to low levels of environmental oxygen. Based on public annotations of the genomes of both morphs, cavefish appear to have lost several hb family members compared to surface fish. We predicted which family members (or duplicates) were differentially lost in cavefish based on structural and phylogenetic analyses. We presume hb gene loss in cavefish is the result of selective pressures maintaining those hemoglobin proteins optimally suited for low oxygen conditions in the cave. This work showcases hb clusters as important tools for understanding adaptation to low oxygen in the natural world, and showcases gene loss as an adaptive evolutionary mechanism.