Selective programs associated with domestication can improve fish production but also can have an impact on broodstock’s genetic diversity. In this study, the genetic diversity of original sources (G0) from wild and cultured bighead catfish populations, as well as the two successive generations (G1 and G2) subjected to selection experiments, was assessed. G0 wild adults were collected in Ca Mau conservation area and G0 cultured fish were from a hatchery in Can Tho. The G1 fish included pure crosses and crossbreeds of G0, while G2 was the offspring of the selected G1. Fin clips from 27 to 29 individuals of each fish group were randomly sampled for genetic analysis. The amplification results using six ISSR primers showed that the genetic diversity was relatively higher in G0 (effective number of alleles Ne from 1.43 to 1.49; heterozygosity He from 0.265 to 0.290) than in G1 (Ne = 1.32±0.04; He = 0.201±0.023) and G2 (Ne = 1.34±0.04; He = 0.216±0.023). Genetic differences increased between the original populations and the descending generations. To reduce the detrimental impacts of low genetic diversity in domesticated bighead catfish in the Mekong Delta, it is recommended that broodstock in later generations should be produced in a larger...