Description: 〈jats:title〉Abstract〈/jats:title〉 〈jats:p〉Tipping points in the Earth system describe critical thresholds beyond which a single component, part of the system, or the system as a whole changes from one stable state to another. In the present-day Southern Ocean, the Weddell Sea constitutes an important dense-water formation site, associated with efficient deep-ocean carbon and oxygen transfer and low ice-shelf basal melt rates. Here, a regime shift will occur when continental shelves are continuously flushed with warm, oxygen-poor offshore waters from intermediate depth, leading to less efficient deep-ocean carbon and oxygen transfer and higher ice-shelf basal melt rates. We use a global ocean–biogeochemistry model including ice-shelf cavities and an eddy-permitting grid in the southern Weddell Sea to address the susceptibility of this region to such a system change for four 21〈jats:sup〉st〈/jats:sup〉-century emission scenarios. Assessing the projected changes in shelf–open ocean density gradients, bottom-water properties, and on-shelf heat transport, our results indicate that the Weddell Sea undergoes a regime shift by 2100 in the highest-emission scenario SSP5-8.5, but not yet in the lower-emission scenarios. The regime shift is imminent by 2100 in the scenarios SSP3-7.0 and SSP2-4.5, but avoidable under the lowest-emission scenario SSP1-2.6. While shelf-bottom waters freshen and acidify everywhere, bottom waters in the Filchner Trough undergo accelerated warming and deoxygenation following the system change, with implications for local ecosystems and ice-shelf basal melt. Additionally, deep-ocean carbon and oxygen transfer decline, implying that the local changes ultimately affect ocean circulation, climate, and ecosystems globally.〈/jats:p〉