The oxidation of sulfides present in mine tailings may generate acidic leachate and result in the discharge of contaminants such as metals, derived from mine wastes into the environment. For mine sites in regions with a humid climate such as the Doyon-Westwood mine, Abitibi, Quebec, acid mine drainage (AMD) is often inhibited using the low gas diffusivity of water to control the oxygen flux reaching the tailings. A management technique of increasing importance is a combined approach of water table level control and the judicious use of a monolayer cover to limit oxygen ingress to sulfidic tailings. The objective of this study was to evaluate the effects of design parameters such as the cover material grain size and thickness, the presence of an anti-evaporation layer, and the position of the water table on the performance of the technique, and to evaluate the long-term oxygen consumption by the low-sulfide cover material. Twelve laboratory columns replicating a monolayer cover made of desulfurized tailings placed over reactive tailings were subjected to monthly wetting–drainage cycles and were monitored for over a year before being dismantled. The cover materials and leachates were chemically analysed to characterize and extrapolate the evolution of water quality, and oxygen movement into the system. The results indicated that the level of the water table was the most important factor influencing the effectiveness of the cover. Furthermore, it appears that although residual sulfides from the cover consumed most of the oxygen flux, this advantage is of short duration (up to 4.7 years). Finally, the risks of leachate contaminated with iron and zinc were identified.