The bivalve Macoma balthica (L.) is a key species of intertidal mudflats in France and Europe. Its natural range has experienced a contraction along the European coastline towards the northeast during the past five decades. This southern boundary shift seems to be correlated with the increased sea surface temperature in the Bay of Biscay (France), a major glacial refugium during the LGM (Last Glacial Maximum, 18000 years ago). In this study, we used one mitochondrial marker (COI) and eight nuclear microsatellite markers to reveal patterns consistent with populations that are close to a glacial refugium. Meridional populations exhibit high genetic diversity, contrary to what is expected from populations at the edge of a species range. In addition, we highlight a barrier to gene flow in the Bay of Biscay populations, near Brittany. So considering (i) the previously reported sensitivity of M. balthica to elevated temperatures, (ii) the genetic isolation of the southernmost populations, and (iii) the importance of this species in the trophic web, the population ecology and genetic structure of this species should be monitored in the context of global warming.