The current work examines the linkage of pronounced winter–summer fluctuations on the nutrient composition with phytoplankton assemblages and mussel toxicity produced by the presence of toxic dinoflagellates. The work was performed at the Óbidos lagoon, a coastal eutrophic ecosystem that is permanently connected to an area characterized by frequent upwelling episodes. The lagoon and adjoining coastal area exhibit recurrent incidents of diarrhetic and paralytic shellfish poisoning. The conclusions are based on: (1) inorganic and organic nutrients at five sites of the lower, middle and upper Óbidos lagoon, and inorganic nutrients at two sites of the adjacent coastal area; biannual campaigns were performed in winter and summer between 2006 and 2010; (2) phytoplankton assemblages at three sites of the lagoon (located at lower and upper areas) in winter and summer of 2009; (3) algae-derived toxicity of wild mussels from the lower lagoon and coastal area, on a 1–2 week time scale, over 2006 and 2009. Nutrient molar ratios in Óbidos lagoon contrast between winter and summer. The lower median ratios DIN:P (31 and 0.8) and Si:P (11 and 3.3) in summer reflect the excess of phosphate. Excess was mainly attributed to phosphorus regeneration in sediments of the upper lagoon with accentuated symptoms of eutrophication. Dissolved organic nitrogen and dissolved organic phosphorus were also higher in summer, particularly in this area. No significant winter–summer differences were recorded for nutrient ratios in the adjacent coastal area. Phytoplankton assemblages pointed to a winter–summer contrast characterized by a shift of non-siliceous-based phytoplankton to diatoms. The toxic dinoflagellate species (Gymnodinium catenatum, Dinophysis cf. acuminata and Dinophysisacuta), presumably imported from the adjacent coast following upwelling episodes in summer, were observed in the lower lagoon. In summer of the two surveyed years, toxins produced by dinoflagellates occurred in mussels from the lower lagoon and coastal area. However, mussel toxicity in the lagoon exceeded values of the coastal area suggesting that high cell density of toxic dinoflagellates resulted from favourable nutrient conditions. We conclude that connectivity between eutrophic lagoons and upwelling systems stimulates the increase of toxic algae and consequently enhancing shellfish toxicity.