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Abstract Transient climate sensitivity is strongly shaped by geographical patterns of ocean heat uptake (OHU). To isolate the effects of uncertainties associated with OHU, a single slab ocean model is forced with doubled CO₂and an ensemble of OHU patterns diagnosed from transient warming scenarios in 12 fully coupled models. The single-model ensemble produces a wide range of Southern Ocean (SO) sea surface temperature (SST) and Antarctic sea ice responses, which are in turn associated with a 1.1–2.0-K range of transient climate response (TCR). Feedback analysis attributes the TCR spread primarily to shortwave effects of low clouds in the Southern Hemisphere (SH) midlatitudes. These cloud changes are strongly positively correlated with storm-track eddy kinetic energy. It is argued that midlatitude clouds (and thus planetary albedo) are remotely driven by SO SST and Antarctic sea ice, mediated by large-scale changes in SH baroclinicity and lower-tropospheric stability. The robustness of this atmospheric teleconnection between SO SST, Antarctic sea ice, and global feedback through midlatitude clouds is supported through additional simulations that explore more extreme SST and sea ice perturbations. These results highlight the importance of understanding physical relationships between SST, sea ice, circulation, and cloud changes in the SH as a pathway to better constraining transient climate sensitivity. Significance StatementAlthough it is well known that Earth’s global-mean surface temperature increases with increasing atmospheric CO₂, there are still significant uncertainties in the temperature and sea ice trends over the Southern Ocean region. Using a climate model, we find that Southern Ocean temperature and Antarctic sea ice changes can result in substantial cloud cover changes over the Southern Hemisphere, which play a primary role in determining the amount of warming in our experiments. We suggest that, in order to reduce uncertainty in future climate change, more work is needed to understand how the climate of the southern polar region can affect the circulation and clouds of the midlatitudes.