Eastern oysters (Crassostrea virginica) have been harvested from U.S. Gulf of Mexico and Atlantic estuaries for centuries. Today, oyster farming is one of the highest valued sectors of aquaculture in the United States, with the Gulf region producing the most oysters (by volume) in 2017. Although eastern oysters are tolerant to a wide range of salinity, long periods of low salinity (<5 ppt) can result in oyster mortality, especially in conjunction with high water temperatures (> 28°C). Triploid oysters, bred to have three sets of chromosomes and faster growth rates, may be even more susceptible to these conditions than diploids (2 sets of chromosomes). Furthermore, broodstock parentage must be taken into account when breeding oysters as there is increasing evidence of divergence in salinity tolerance among Gulf of Mexico oyster populations even across a narrow geographic range. The industry could benefit from research efforts to investigate the effects of ploidy and broodstock parentage on the field performance (growth and mortality), as well as physiological parameters of oysters exposed to moderate and low salinity conditions. Studies can also incorporate information such as intracellular metabolite gradients (cellular level) and karyotype (chromosomal level) to get a more complete view of how multiple organizational levels interact with oyster bioenergetics and field performance (organismal level).