We explore and evaluate various processes that could drive the variations in the volume mixing ratio (VMR) of atmospheric O2 observed by the quadrupole mass spectrometer (QMS) of the Sample Analysis at Mars (SAM) instrument suite on the Mars Science Laboratory (MSL) Curiosity rover. First reported by Trainer et al. (2019), these ∼20% variations in the O2 VMR on a seasonal timescale over Mars Years 31–34, in excess of circulation and transport effects driven by the seasonal condensation and sublimation of CO2 at the poles, are significantly shorter than the modeled O2 photochemical lifetime. While there remains significant uncertainty about the various processes we investigated (atmospheric photochemistry, surface oxychlorines and H2O2, dissolution from brines, and airborne dust), the most plausible driver is surface oxychlorines, exchanging O2 with the atmosphere through decomposition by solar ultraviolet and regeneration via O3. A decrease in O3 from increased atmospheric H2O would reduce the removal rate of O2 from the atmosphere to form oxychlorines at the surface. This is consistent with the tentative observation that increases in O2 are associated with increases in water vapor. A lack of correlation with the local surface geology along Curiosity’s traverse within Gale crater, the nonuniqueness of the relevant processes to Gale crater, and the short mixing timescales of the atmosphere all suggest that the O2 variations are a regional, or even global, phenomenon. Nonetheless, further laboratory experiments and modeling are required to accurately scale the laboratory-measured rates to Martian conditions and to fully elucidate the driving mechanisms.