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The Eastern Desert of Egypt represents a remote arid area which is scarce in water resources. The area is characterized by many mining sites to exploit the phosphate deposits; thus, these activities can generate groundwater contaminants. The main objective of the present study is discussing the effect of the mining activities and phosphate bearing rocks on groundwater. The obtained results pointed out that the water bearing formations can be distinguished as Quaternary alluvial, Oligocene sandstone, Campanian phosphate limestone (Duwi Formation), and Precambrian basement rocks. Some of the investigated groundwater shows relatively high concentrations of trace elements compared to other samples, such as Pb, Zn, Cu, Cr, Ni, and Sr. This is consistent with the analyses of phosphate rocks which are also enriched in the same trace elements. The high groundwater salinity is due to evaporation, limited re-charge, and leaching of salts in rocks. The results of speciation modeling reveal that majority of groundwater samples are supersaturated with calcite, aragonite, and dolomite, and some samples are also at equilibrium or supersaturated with hydroxyapatite. The groundwater quality in the study area evaluated for human drinking, livestock and poultry domestic, and industrial purposes is not suitable in most wells. It is obvious that the groundwater contamination occurs when drilling wells penetrate the phosphate bearing beds and not only at mining activity sites. Therefore, it is recommended to avoid any groundwater exploration from the Duwi Formation and also select the drilling sites outside the mining areas.