In the Alvarado Lagoon System (ALS) in south-central Veracruz on Mexico's gulf coast, the blue land crab, Cardisoma guanhumi, a semi-terrestrial crustacean species, represents an important fishery resource, but one that is subject to overexploitation and habitat destruction. Identifying genetic diversity and the genetic unit are required to establish efficient conservation strategies. The present study's goal was to assess the genetic structure and degree of genetic diversity of C. guanhumi populations along the ALS. A fragment of the D-loop region of the mtDNA (750 bp) and a partial sequence of the COI gene (580 pb) was sequenced for 120 specimens collected at four sites in the ALS. Genetic diversity indices were estimated for each marker. The study sites' gene flow was estimated, as was the effective population size and the mutational rate for each locality. A haplotype network was built to estimate the gene genealogies of the populations. A Tajima's neutrality test, Fu tests, and mismatch analysis were performed to detect demographic expansion. Results show that this C. guanhumi population has high genetic diversity with a large gene flow among the localities studied and expanded during the recent evolutionary past. All haplotypes from both markers are novel for the species, according to the NCBI GenBank. The high genetic diversity and genetic connectivity among sites suggests that the size of blue crab populations in the ALS has not been drastically affected by past exploitation. Finally, management strategies are proposed to protect the species.