Secondary sulfate minerals are common throughout the sedimentary deposits of Mount Sharp, located within Gale crater on Mars. However, the source of sulfate (SO42- ) and past climatic conditions during their formation are not well understood. Therefore, we investigated the S34S, S18O, and S2H of gypsum veins and other Mg- and Ca- sulfates forming as salt crusts and cement within the shallow sediments of the Rio Puerco watershed in central New Mexico. The S34S values of vein gypsum and acid-soluble SO42- (cement) varied over the same range (-33.3 to -12.9 %o and -34.6 to -12.1 %o, respectively), which was similar to the S34S of bedrock sulfide minerals (-37.4 to -5.9 %o). This implies that sulfide oxidation is the main source of SO42- in the Rio Puerco aqueous system. The measured S18O values of SO42- (-8.9 to +3.1 %o) as well as S18O and S2H values of gypsum hydration water (-8.9 to +0.6 %o, and -112 to -82 %o, respectively) overlapped with the isotope composition of local meteoric precipitation, suggesting that sulfide oxidation to SO42- and gypsum formation have occurred under semi-arid climate conditions. The isotope results suggest the top-down infiltration of meteoric water leads to leaching of SO42- , Mg+, and Ca2+ from bedrock sulfide weathering followed by abundant formation of Mg- and Ca-sulfates in surface deposits and gypsum veins with depth. Because of spatial and mineralogical similarities in the secondary Mg- and Ca-sulfate mineral occurrences, we hypothesize that chemical weathering of sulfide minerals could have been the main source of SO42- in the aqueous system of Gale crater.