In this work we study the response of phytoplankton and potentially harmful species to river inflows in a coastal area of eastern Mediterranean, within the context of environmental status assessment suggested by the European Commission’s Water Framework Directive (WFD, 2000/60/EC) and Marine Strategy Framework Directive (MSFD, 2008/56/EC). The spatio-temporal distribution of phytoplankton communities and biomass (as chlorophyll a), potentially harmful species, nutrient levels, dissolved oxygen, salinity and temperature were studied. A marginal good to moderate physicochemical status was assigned in the delta of Spercheios river that outflows in Maliakos Gulf. Silicates and nitrates were indicated as proxies of freshwater influence in Maliakos Gulf, whereas ammonium, nitrites and phosphates as proxies of pollutants from non-point sources. Phytoplankton biomass and abundances reached high levels throughout Maliakos Gulf inter-seasonally. High silicates favored the dominance of Diatoms. The potentially harmful species were blooming frequently, with higher levels in the estuary, and they were associated with low salinity, showing the riverine influence on them. Pseudo-nitzschia was the most frequent potentially harmful genus with an interesting strong linkage with low silicates and nitrates. Maliakos Gulf demonstrated an overall mesotrophic condition and failed to achieve good ecological status.