Popularly known as blue land crab, Cardisoma guanhumi is heavily exploited as food and considered as an important economic resource in Brazil. In recent decades, the species has experienced a sharp population decline by the loss and/or degradation of its natural habitat and overfishing. The present study aimed to investigate the genetic variation and connectivity among 154 specimens of C. guanhumi sampled along the coast of Pernambuco in five different levels of tropical mangroves conservation. Nine ISSR primers were used for assessing the genetic variation of the species. The genetic diversity observed in C. guanhumi was high reinforcing the condition of a resilient species, indicating a good conservation status of this resource in Pernambuco. The hypothesis of panmixia was rejected in favour of a heterogeneous distribution of the genotypes of C. guanhumi (ФST = 0.19) despite the high gene flow observed in the study region. Such difference could be attributed to the candidate loci being under positive selection and differentially distributed between the geographic regions assessed. The genetic structure showed a pattern of fine-scale genetic structuring better fitted to a model of selection-mediated geographic cline. Cluster analysis and candidate loci under positive selection suggested that the populations of C. guanhumi in the North-central and South coasts of Pernambuco might be different management units and must be managed independently. In conclusion, exhaustion of natural stocks upon which fishing is totally dependent will lead to serious ecological and sociocultural impacts.