Sediment heavy metal pollution and water quality were examined at Nestos River and its estuary, a heavily modified ecosystem due to the construction of two hydropower dams (Thissavros and Platanovrisi). The dam operation created three systems with different characteristics: the upstream, the downstream parts and the reservoirs. Surface sediments and water samples were collected from 25 station in total (6 from the main river, 2 from reservoirs and 17 from the estuary) in order to examine the system degradation. The concentrations of five metals (Cu, Cd, Ni, Cr and Pb) were determined with the use of GFAA technique, while the FIAS technique was used for Hg determination in a Perkin-Elmer AAS-800 atomic absorption instrument. Several physicochemical parameters (temperature, conductivity, D.O., pH) were measured in situ and laboratory analysis were undertaken for the determination of six nutrients (NO3, NO2, NH4, NH3, SiO2 and PO4). The heavy metal pollution assessment was achieved with the use of several indices widely used in the literature (i.e. PLI, CD, Igeo, PERI), whereas water quality was determined using the CCME-WQ index (Canadian Water Quality Guidelines). The results showed that according to CD index moderate metal pollution in sediments were determined in both reservoirs and at the coastal area and considerable ecological risk was found according to PER index in Platanovrisi reservoir. PLI revealed zero pollution and Igeo showed minimal Pb pollution for all areas. Regarding water quality, the application of CCMEWQ index demonstrated good-excellent water quality at the upstream, downstream and estuary areas, fair quality inside the reservoirs and marginal quality at the bottom of Platanovrisi mainly due to low D.O. and high PO4 concentrations.