A multidisciplinary survey was carried out on the quality of water and sediments of the estuary of the Sele river, an important tributary of the Tyrrhenian Sea, to assess anthropogenic pressures and natural variability. Nine sediment sites were monitored and analyzed for granulometry, morphoscopy, benthic foraminifera and ostracod assemblages, heavy metals, and polycyclic aromatic hydrocarbons. Surface water was assayed for ionic composition and phytoplankton biomass. Total organic carbon (TOC) and total nitrogen (TN) in sediments were higher in the inner part of the estuary (IE), up to 12.7 and 0.7% because of anthropic influence. In waters, N-NH₄, N-NO₃, and P_tot. were high, with loads of P_tot in IE exceeding ~fourfold the limit. Here, it was also observed that the highest primary production was Chl-a, 95.70 µg/L, with cryptophytes, 37.6%, and diatoms, 33.8%, being the main phytoplanktonic groups. The hierarchical analysis split the estuary into two areas, with marked differences in anthropic pollution. Waters were classified as poor–bad level with respect to the content of nutrients. Sedimentological assay reveals littoral erosion and poor supply of river sandy sediments. The erosion environment is confirmed by the presence of meiobenthic recent marine forms intrusion inside the river. All these data reveal the fragility of the estuary and the need of urgent remediation actions.