The importance of identifying and quantifying subsurface geochemical reaction rates and processes by monitoring and modeling CO2 and O2 concentrations is well established. These parameters, however, are typically studied independently under presumed steady-state conditions. Here we present models of seasonally variable vadose zone CO2 and O2 concentrations that use δ18O of O2 as a constraint to create a dynamic link between these three parameters under transient conditions. The gas transport modeling was used to quantify the controls of biogeochemical processes and parameters (i.e., temperature and moisture content) on vadose zone distributions of CO2 and O2 gas concentrations. The investigation was conducted on a 3-m-thick, unvegetated, fine-sand vadose zone located in northern Alberta, Canada (56°40′N, 111°07′W). Using the modeled molar ratio of surface fluxes for O2 and CO2, the change in reaction rate for a temperature change of 10°C (Q10), moisture content at maximum reaction rates, and biogeochemical discrimination against consumption of 18O16O (αk), we determined that organic C oxidation by microbial respiration was the predominant mechanism consuming O2 and producing CO2. The mean αk was determined to be 0.973, suggesting that subsurface respiration was via the alternative oxidase pathway, which may be common in cold climates. Modeling revealed that the moisture content of a moist, surficial clayey sand layer (0.1–0.3 m thick) had a dramatic effect on pore-gas CO2 and O2 concentrations and on δ18OO2. The vadose zone in this study was at an unvegetated site to simplify the model application; however, it can be modified to include root respiration and applied to natural vadose zones to help quantify the role of subsurface respiration in global O2 and C budgets.