Cold-water corals form vast reefs that are highly valuable habitats for diverse deep-sea communities. The deep ocean is, however, warming and it’s therefore essential to assess the resilience of cold-water corals to future conditions. Here we investigate the effects of elevated temperatures on the cold-water coral Lophelia pertusa (now named Desmophyllum pertusum) from the north east Atlantic Ocean at the holobiont level, the coral host and its microbiome. We show that at temperature increases of + 3 and + 5°C, L. pertusa exhibits significant mortality concomitant with changes in its microbiome composition. In addition, a metagenomic approach revealed the presence of genes markers for bacterial virulence factors suggesting that coral death was due to infection by pathogenic bacteria. Interestingly, different coral colonies had different survival rates, as well as colony-specific microbiome signatures, indicating strong colony variability in response to warming waters. Our results suggest that L. pertusa can only survive a temperature increase of < 3°C over the long term. Regional variations in deep-sea temperature increase should therefore be considered in future estimates of the global distribution of cold-water corals.