We analyze the variability of air-sea fluxes of carbon dioxide and oxygen in the Southern Ocean during the period 1993–2003 in a biogeochemical and physical simulation of the global ocean. Our results suggest that the nonseasonal variability is primarily driven by changes in entrainment of carbon-rich, oxygen-poor waters into the mixed layer during winter convection episodes. The Southern Annular Mode (SAM), known to impact the variability of air-sea fluxes of carbon dioxide, is also found to affect oxygen fluxes. We find that El Niño–Southern Oscillation (ENSO) also plays an important role in generating interannual variability in air-sea fluxes of carbon and oxygen. Anomalies driven by SAM and ENSO constitute a significant fraction of the simulated variability; the two climate indices are associated with surface heat fluxes, which control the modeled mixed layer depth variability. We adopt a Lagrangian view of tracers advected along the Antarctic Circumpolar Current (ACC) to highlight the importance of convective mixing in inducing anomalous air-sea fluxes of carbon dioxide and oxygen. The idealized Lagrangian model captures the principal features of the variability simulated by the more complex model, suggesting that knowledge of entrainment, temperature, and mean geostrophic flow in the mixed layer is sufficient to obtain a first-order description of the large-scale variability in air-sea transfer of soluble gases. Distinct spatial and temporal patterns arise from the different equilibration timescales of the two gases.