Sewage discharges constitute severe stress in freshwater ecosystems. The Ramalhoso River belongs to the Tagus River watershed and was chosen for a pilot study on the impact of wastewaters discharges in a freshwater ecosystem and its ability for self-depuration. Twelve water samples were collected along the river and were georeferenced. The first point is located upstream of the first discharge point, the second one corresponding to the discharge flow, and all the other samples located downstream of secondary inflows at approximately equal distances. Three sampling campaigns were conducted during the rainy winter (January), the intermediate conditions (March), and the dry season (June). The following chemical parameters were analyzed: biochemical oxygen demand for 5 days (BOD 5 ), dissolved oxygen concentration (DO), total phosphorus (P total ), total nitrogen (N total ), pH, temperature, total suspended solids (TSS), microbiological parameters (MP), and flow determination. Dissolved oxygen, BOD 5 , and TSS were used as indicators of environmental pollution. A coupled hydrodynamic and water dispersion model simulated different pollution scenarios using the QUAL2kw software to construct a water quality model. The simulation results are consistent with field observations and demonstrate that the model has been correctly calibrated, allowing feasibility studies of different treatment schemes and the development of specific monitoring activities.