The Cuatrocienegas area is useful for the investigation of the effect of groundwater extraction in the Chihuahuan freshwater xeric ecoregion. It has been investigated at this time using a selection of geochemical indicators (major, minor and trace elements) and delta S-34 data, to characterize the origin of groundwater, the main geochemical processes and the mineral/groundwater interactions controlling the baseline geochemistry. The area is composed of limestones of Mesozoic age, with a composite thickness of about 500m, overlaid by basin fill (poorly consolidated young sediments). Substantial water extraction and modification of natural discharges from the area along the last century have produced a detrimental impact on ecosystem structure and function. Water-rock interactions, mixing and evaporative processes dominate the baseline groundwater quality. Natural recharge is HCO3-Ca type in equilibrium with calcite, low salinity (TDS<500mg/L), Cl- lower than 11mg/L and average Li+ concentration of 0.005mg/L. Along the groundwater flow systems, delta S-34 evidence and mass transfer calculations indicate that Cretaceous gypsum dissolution and dedolomitization reactions adjust water composition to the SO4-Ca type. The increase of water-rock interaction is reflected by Cl- values increase (average 68mg/L), TDS up to about 1500mg/L and an average Li+ concentration of 0.063mg/L. Calculations with chemical geothermometers indicate that temperature at depth could be at maximum of 15-20 degrees C higher than field-measured temperature for pozas. After groundwater is discharged to the surface, chemical evolution continues; water evaporation, CO2 degassing and precipitation of minerals such as gypsum, calcite and kaolinite represent the final processes and reactions controlling water chemical composition.