The Adriatic Sea, being a semi-closed and shallow basin, is more sensitive to anthropogenic impact than other areas of the Mediterranean Sea. Given the crucial role of meiofauna in the marine ecosystems, temporal series of data on this benthic assemblage are fundamental to give new insights into the health status of this basin. A data set (decade 2002–2012) on the meiofauna of two river mouths (Foglia and Metauro) close to a Natural Park (Monte San Bartolo, Central Adriatic Sea) has been analysed and related to several environmental parameters. In particular, changes in the meiofaunal structure, abundance and diversity have been investigated in order to evaluate possible variations of ecological quality status (EQS), in accordance with the Water Framework Directive. The structure of the meiofaunal assemblage appeared significantly different in the period studied, with a higher abundance of annelids in 2002 and an increase of nematodes in the following sampling campaigns. Among the faunal parameters, the Shannon and Pielou indices suggested a decline of the EQS over time, likely mainly due to the negative effect of chlorophyll-a peaks, which may highlight the influence of eutrophication phenomena and an enhancement of the organic matter supply. The lowering of the EQS of the study area suggests the need to intensify management and conservation efforts in the coastal systems, and supports the use of the meiofaunal assemblage as a useful bioindicator.