CO2 + O2 is a relatively mature, neutral, in situ leaching process that has been widely used. However, the decrease in uranium concentration in the leaching solution during production has become a serious problem in the western section of the south ore belt of the Shihongtan deposit in Xinjiang, China. In order to solve this problem, mineralogy and batch tests were carried out to explore the reason for the low uranium resource leaching efficiency and determine better leaching process parameters. A total of 16 tests were carried out under different conditions of CO2/O2 ratios and HCO3− concentrations. The results show that: (1) The uranium minerals in the ore were mainly pitchblende and titanium-bearing uranium mineral. Part of the uranium resources were mixed in quartz, which were difficult to activate and recover. The high content of calcium carbonate and clay minerals in ore and the high TDS (total dissolved solid) content in groundwater would cause a reduction in porosity. (2) According to the uranium concentration and uranium leaching rate, a better leaching efficiency was obtained when the pH was lower than 6.6, and the HCO3− concentration was 800 mg/L. This result could serve as a reference for production in other similar mines.