Marine Synechococcus, together with Prochlorococcus, contribute to a significant proportion of the primary production on Earth. The spatial distribution of these two groups of marine picocyanobacteria depends on different factors such as nutrients availability or temperature. Some Synechococcus ecotypes thrive in mesotrophic and moderately oligotrophic waters, where they exploit both oxidized and reduced forms of nitrogen. Here, we present a comprehensive study, which includes transcriptomic and proteomic analyses of the response of Synechococcus sp. strain WH7803 to nanomolar concentrations of nitrate, compared to ammonium or nitrogen starvation. We found that Synechococcus has a specific response to nanomolar nitrate concentration that differs to the response showed under nitrogen starvation or the presence of standard concentrations of either ammonium or nitrate. This fact suggests that the particular response to the uptake of nanomolar concentration of nitrate could be an evolutionary advantage for marine Synechococcus against Prochlorococcus in the natural field.