Acid in situ leaching (AISL) is a subsurface mining approach suitable for low-grade ores which does not generate tail-ings, and has been adopted widely in uranium mining. However, this technique causes an extremely high concentra-tion of contaminants at post-mining sites and in the surroundings soon after the mining ceases. As a potential AISL remediation strategy, natural attenuation has not been studied in detail. To address this problem, groundwater collected from 26 wells located within, adjacent, upgradient, and downgradient of a post-mining site were chosen to analyze the fate of U(VI), SO42-, delta 34S, and delta 238U, to reveal the main mechanisms governing the migration and atten-uation of the dominant contaminants and the spatio-temporal evolutions of contaminants in the confined aquifer of the post-mining site. The delta 238U values vary from -0.07 %o to 0.09 %o in the post-mining site and from -1.43 %o to 0.03 %o around the post-mining site. The delta 34S values were found to vary from 3.3 %o to 6.2 %o in the post-mining site and from 6.0 %o to 11.0 %o around the post-mining site. Detailed analysis suggests that there are large differences between the range of isotopic composition variation and the range of pollutants concentration distribution, and the es-timated Rayleigh isotope fractionation factor is 0.9994-0.9997 for uranium and 1.0032-1.0061 for sulfur. The isotope ratio of uranium and sulfur can be used to deduce the migration history of the contaminants and the irreversibility of the natural attenuation process in the anoxic confined aquifer. Combining the isotopic fractionation data for U and S with the concentrations of uranium and sulfate improved the accuracy of understanding of reducing conditions along the flow path. The study also indicated that as long as the geological conditions are favorable for redox reactions, natural attenuation could be used as a cost-effective remediation scheme.