The influence of the Sinú River and the Caribbean Sea over the Cispatá lagoon system was studied through annual and interannual analysis, as well as the tendency of hydrological (precipitation, discharge), and marine (SST, level) time series. The hydrological series were correlated with ONI, NAO and PDO macroclimatic indices, and, from data logging of flow stations down of Urrá I dam, their effects over the lagoon system were studied. No significant correlation between the precipitation and ENSO was found. The flow of the river basin highlands contribute with 50% of the one released. The flow coming into the lagoon system displayed a monomodal cycle. Positive flow anomalies were associated with La Niña, negative ones with El Niño. We found that the regulation effect on the flow by Urrá I is noticeable in the Angostura de Urrá, Pasacaballo, and Caño Grande stations, whereas in the Cotoca Abajo station it is not substantial. The sea level and the SST registered a 25 cm rise in 44 years, and one of 0.6 °C in 20 years, respectively. Four prospective scenarios on the river – sea influence over the lagoon system were presented, considering the sea level rise. The first two scenarios suppose that the communications between the Sinú River and the lagoon system will last; and the following two that one of the two arms of the river that feed the system will clog.