The stable isotopes of water were used to improve the determination of the groundwater budget of the deep Saharan “Continental Intercalaire” (CI), a deep confined aquifer. Mixing processes between the CI and shallower aquifers have been described in several regional studies over the last few decades, based on observed isotopic differences between local water masses. Here, we improve the quantitative determination of the discharge flux of this aquifer in one of its main outlet regions, the Djeffara plain in Tunisia, based on geostatistics and a simple mass balance mixing model, applied before and after the beginning of extensive pumping in the 1970s. First, the average values of δ18O and δ2H were precisely documented in the mixing zone between CI water and the local recharge, based on conditional simulations using spatially distributed isotopic data. Together with the available estimate of local recharge and conservative hypotheses on the isotopic end-members, we estimate the discharge flux of the CI in the Djeffara plain at 1.78 ± 1.03 m3 s−1 in 1970, probably near natural steady-state, reduced to 1.02 ± 0.58 m3 s−1 in 2004 under strong anthropogenic pressure, related to the drastic increase in pumping rates in the deep CI aquifer during this period. Considering the general groundwater budget over the entire CI aquifer, we estimate a recharge value of 5.13 m3 s−1, or 6.5 mm yr−1 over the 25,000 km2 of recharge area in the Saharan Atlas. This value is in line with the evaluation of 2.1 mm yr−1 obtained recently from the GRACE satellite gravity data for the overall outcrops considering that recharge occurs mostly in the Atlas region.