Climate models report that the environmental changes resulting from excess CO2 and heat absorption by the ocean already reach many deep-ocean margins, basins, and seas. Decadal monitoring programmes have confirmed significant warming and deoxygenation trends down to the abyss, which combine with CO 2 -enriched, more corrosive conditions. Although the resolution of current models does not account for the typical mesoscale seafloor heterogeneity, cumulative impacts on biodiversity and productivity hotpots are anticipated. The growing interest in deep-sea resource exploitation has shed light on the lack of knowledge about current climate-driven disturbance and potential cumulative threats at great depth. Assessing the sensitivity of deep-sea ecosystems to temperature increase combined with oxygen and resource decline is emerging as a growing challenge. The natural patchiness of deep-seafloor habitats and associated deep-sea diversity patterns inform about environmental constraints over space, but the temporal dynamics of these systems is not well known. Experimental studies are required to assess the physiological limits and explore the adaptation and acclimation potential of foundation species exposed to various forms of abiotic stress. The case of cold-water corals is particularly illustrative of the potential synergistic effects of climate stressors, including warming, acidification, deoxygation, and reduced food availability. Addressing ecosystem vulnerability also requires dedicated monitoring efforts to identify the current and future drivers of climate-change impacts on deep-sea habitats. United Nations policy objectives for protected high-sea biodiversity and healthy oceans and seas drive the momentum towards better climate-change forecasting over the ocean-depth range and related integrated observing strategies.