Cold-water corals form vast reefs that are highly valuable habitats for diverse deep-sea communities. The deep ocean is, however, getting warmer, and models predict that the temperature of the Atlantic Ocean will further increase by up to 3°C by the end of the century. Understanding the response of cold-water corals to ocean warming is therefore essential to assess their resilience to future water temperatures. Here, we investigate at the holobiont level, the coral host and its associated microbiome, the effects of elevated temperatures on the reef-forming cold-water coral Lophelia pertusa (now named Desmophyllum pertusum) from the north east Atlantic Ocean. We show that at temperature increases of +3 and +5°C, L. pertusa exhibits significant mortality concomitant with changes in its microbiome. A metagenomic approach revealed the presence of genes markers for bacterial virulence factors suggesting that coral death was due to infection by pathogenic bacteria. Differences in survival were observed between L. pertusa colonies, as well as colony-specific microbiome signatures, indicating strong colony variability between colonies in response to warming waters. We hypothesize that L. pertusa, regardless of their ocean of origin, can only survive a temperature increase of < 3°C over a long period of time. Regional variations in deep-sea temperature increase should therefore be taken into account in future estimates of the global distribution of cold-water corals.