European white oaks are long-lived species and are one of the most important foundation species in European temperate forests. In the context of global climate change, droughts, heat waves and emerging biotic enemies such as insects and pathogens are putting populations and ecosystems at risk. Specialized metabolitesplay a key role in tree defenses against natural enemies and protection against abiotic stresses such as UV exposure and drought. Here, we used high-throughput MS-based metabolomics to explore the natural variation of over 100 leaf specialized metabolites in 25 sessile oaks from nine provenances, all growing in a common garden in France. Among the metabolites analyzed, which included mostly hydrolysable tannins and flavonoïds, very few displayed differentiation among provenances, of which 22 displayed clear bimodal distributions with phenotypic classes present at balanced frequencies in all provenances. To investigate thegenetic bases of leaf specialized metabolites, we performed whole-genome low coverage (~10X) sequencing of all individuals phenotyped in order to perform genome-wide association mapping. We identified over 1.6 million genome-wide SNPs, which revealed little genetic differentiation among provenances. Linkagedisequilibrium (r2) decayed below 0.2 over 2 kb, suggesting that our genome-wide SNPs were sufficient to capture most genetic variation. We performed a genome-wide association analysis for the leaf specialized metabolites, identified candidate genes and checked for signatures of selection along the genome. Our resultssuggest that (i) oak provenances display extensive variation for leaf specialized metabolites, (ii) this variation is to a great extent genetically determined, and (iii) variation of individual metabolites is governed by few major loci.< Réduire