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Abstract One of the main challenges in coral reef conservation and restoration is the identification of coral populations resilient under global warming. Seascape genomics is a powerful tool to uncover genetic markers potentially involved in heat tolerance among large populations without prior information on phenotypes. Here, we aimed to provide first insights on the role of candidate heat associated loci identified using seascape genomics in driving the phenotypic response of Acropora millepora from New Caledonia to thermal stress. We subjected 7 colonies to a long-term ex-situ heat stress assay (4 °C above the maximum monthly mean) and investigated their physiological response along with their Symbiodiniaceae communities and genotypes. Despite sharing similar thermal histories and associated symbionts, these conspecific individuals differed greatly in their tolerance to heat stress. More importantly, the clustering of individuals based on their genotype at heat-associated loci matched the phenotypic variation in heat tolerance. Colonies that sustained on average lower mortality, higher Symbiodiniaceae/chlorophyll concentrations and photosynthetic efficiency under prolonged heat stress were also the closest based on their genotypes, although the low sample size prevented testing loci predictive accuracy. Together these preliminary results support the relevance of coupling seascape genomics and long-term heat stress experiments in the future, to evaluate the effect size of candidate heat associated loci and pave the way for genomic predictive models of corals heat tolerance.