Increasing intensity of storms, typhoons, and sea level rise in conjunction with high water demand, especially for agriculture, in dry seasons in the Red River Delta may have led to seawater intruding deeper into the rivers’ estuaries. Given that losses of agricultural productivity and shortages of freshwater resources are projected, a reliable early warning of salinity invasion is, therefore, crucially needed. To evaluate the impact of salinity variations on riverine ecosystems, distribution patterns of meiofauna were examined at 20 stations along the Van Uc River continuum in the dry season. Meiofaunal richness indices were higher in the estuary and slightly decreased upriver. Nematoda was the most dominant taxon in salty stations, while Rotifera was more abundant in the less salty ones. A multiple variate analysis showed a strong interplay among salinity, nutrients, and pore water conductivity, which shaped the meiofaunal distribution. The inclusion of pore water salinity, nutrients, and meiofaunal community structure indicated a greater extent of the saline ecosystem in the estuary, posing a greater risk of freshwater salinization. Our results highlight the potential role of meiofauna as bioindicators but also call for a reformation of salinity assessment for better freshwater conservation and management.