We present depth profiles of Cd isotopes and concentrations from the Southern Ocean at four stations in the Atlantic sector along the Greenwich Meridian (47°S to 68°S) located across the main Antarctic frontal zones and productivity belt. The vertical profiles of Cd concentration typically show low values in surface waters, elevated values at intermediate depths, reflecting remineralization of sinking particulate organic matter, and constant values in deep waters. The surface-to-deep isotopic gradient shows “heavy” Cd isotope signatures in the mixed surface layer, becoming more pronounced northward, with values up to ɛ112/110Cd of around +4.1 in the Subantarctic sector of the Southern Ocean. Deep Antarctic waters display a uniform and “light” ɛ112/110Cd of +1.18 ± 0.38 and Cd concentrations of 0.761 ± 0.101 nmol/kg (n = 23, 2SD). Intermediate waters are characterized by ɛ112/110Cd lying between those of surface and deep waters, with a constant value of about +0.8 in the High Nutrient Low Chlorophyll sector and a notably higher value of +2.3 in the Subantarctic sector. The Cd isotope fractionation in the Southern Ocean closely follows a simple closed-system Rayleigh model, in which biological uptake of Cd imparts the ɛ112/110Cd signature to the surface layer while that of deep waters is determined by the flux of regenerated isotopically-light Cd from sinking organic matter from the surface ocean and the degree of mixing of distinct water masses. The vertical gradient documented for Cd isotopes and nutrient ratios, along with the meridional gradient in surface waters, highlights the important role played by upwelling in the Southern Ocean in closing the meridional overturning circulation via the export of Antarctic intermediate and mode waters which have a distinctive chemical (low Cd:P) and Cd isotope (“heavy”) signature. The combined Cd–Zn isotope systematics provide evidence for a strong link between the magnitude of biological Cd stable isotope fractionation and Zn availability in the contrasted nutrient and ecological regimes of the Southern Ocean. Substitution of Cd for Zn in the enzyme carbonic anhydrase appears to be the driving mechanism for Cd isotope fractionation in the Antarctic Circumpolar Current, while an “excess-uptake” mechanism seems to predominate in the Weddell Gyre. Our study highlights some of the complexities of the biogeochemical cycling of Cd in the oceans. Nevertheless, systematic variations in Cd isotopic compositions with water mass distribution in the Southern Ocean suggest that Cd isotopes could, with some caveats, be useful tracers of changes in past nutrient utilization and deep water circulation.