Seasonal and inter-annual patterns of hydrological variation determine different salinity regimes inside the Patos Lagoon estuarine region, southern Brazil. Throughout two environmentally distinct years (2000 and 2006), macrobenthic samples were taken seasonally from a 14 m deep main channel region, at nine monitoring sites, using a van Veen grab (0.078 m2). In order to keep the Patos Lagoon main access channel at constant navigable depths, the Rio Grande Harbour Superintendence periodically executes maintenance dredging operations on this infralittoral area, but our multivariate analyses evidenced no significant difference between dredged and non-dredged sites regardless the year. Among the abiotic parameters analyzed here (temperature, percentage of fine sediments and salinity), the later was evidenced to be highly correlated to the biological data. Reductions in density and/or changes in the species composition could both be attributed to a natural macrobenthic response related to environmental variations. Along the year 2000 high salinity values decreased constantly through seasons to almost limnetic condition in spring, reducing diversity and abundance of marine species and densities of the dominant gastropod species Heleobia australis. On the other hand, salinity values along the year 2006 revealed the maintenance of brackish waters throughout seasons, favoring the input and survival of marine species from coastal adjacent areas inside the estuary, raising its macrobenthic diversity mainly by mollusks and polychaete worms.