During drought periods, the razor clam Solen cylindraceus is the dominant bivalve in the St Lucia estuarine system, although restricted to its South Lake region. However, with the recent onset of a wet phase, the mussel Brachidontes virgiliae has become widespread and overwhelmingly dominant throughout the system. The salinity tolerance of B. virgiliae is here determined using both rapid and gradual changes in salinity. Mussels were collected at Esengeni in the Narrows (salinity ≈ 0) and Lister's Point in False Bay (salinity ≈ 20). Mortalities were recorded for animals exposed to a sudden change in salinity using 8 different treatments, ranging from 0 to 70. Additionally, animals were exposed to a gradual change in salinity, using treatments that exceeded the minimum and maximum salinities mussels were previously able to tolerate. In all four experiments, animals were able to tolerate salinity levels up to 20. However, a wider salinity tolerance, up to 50, was shown by animals collected from Lister's Point and those gradually acclimated to test conditions. With an increase in flood events predicted for this region, it is imperative to understand how key species may be affected. During wet phases B. virgiliae becomes ubiquitious throughout Lake St Lucia and it is unlikely that the species will disappear from the system, even if floods escalate in the future, as it has an ability to withstand near-freshwater conditions. During dry periods, however, the mussel will be concentrated in the Narrows (oligohaline to limnetic conditions), especially if an inverse salinity gradient with hypersaline conditions prevails within the system.