In the Kebili region of southern Tunisia, there is increasing demand of water from the Lower Cretaceous Continental Intercalaire (CI) aquifer and the Upper Cretaceous-Miocene Complex Terminal (CT) aquifer. The CI aquifer, given limited low recharge of water and increasing amounts of water extraction, has suffered intense overexploitation since the year 2000. Currently, the sustainability of CI resources is threatened by oil and brine contamination detected at a number of water wells in the Kebili region. Hydrocarbon pollution of the aquifers seems to be ubiquitous because the groundwaters sampled in El Fedjej and Nefzaoua basins exhibit bad water quality according to a number of toxicity indices. Geochemical data indicate that, on a regional scale, groundwater quality, salinity, and dissolved element concentrations are best correlated to petroleum contamination-extraction and to aquifer vulnerability to human perturbations rather than to multiple interactions within the hydrogeological system of the region. The analyses of petroleum compounds in sampled waters indicate that these waters are most consistent with increasing concentrations of organic pollutants; the organic matter is crude and unaltered, testifying to continuous flows of contaminants. The brine contamination, however, is limited to the Djemna water well where the water exhibits a salinity of 20 g L. Combined, these findings suggest that groundwater composition in CI water wells in Kebili field is influenced by the migration of hydrocarbons and brine-enriched waters through fractures, and (or) by aquifer decompression.