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The Santa Lucía River Basin Trough is located in the southern sector of the Eastern Republic of Uruguay and has an area of almost 6,000 km2. In this work, the depth to the basement in the SW sector of the Santa Lucia Basin (SLB) was determined, using geophysical methods of exploration. The interest of exploring this geological basin is to determine its depth, recognizing the possible existence of deep aquifers, and the feasibility of hydrothermalism. For this reason were acquired, processed, inverted, and interpreted 10 magnetotelluric (MT) soundings. A 3D inversion based on the ModEM code was performed, and a 2D inversion (NLCG) of the invariant determinant along a profile that crosses the study area was carried out; their comparison yields similar resistivity and structural models results. The resistivity modeling was complemented with a Bouguer anomaly map created from a gravimetric database of 157 stations. Our geophysical results indicate that the Santa Lucia trough deepens toward the E-NE, reaching sedimentary thicknesses that may exceed 950 m. Outside the studied sector, its depth increases according to the gravity minimum, toward the NE of the area. Therefore, sandy or deep fractured episodes could harbor hot springs, whose temperature, considering the normal geothermal gradient of 30 °C/km, would approximately be in the range of 36–40 °C. [ABSTRACT FROM AUTHOR]