Increasing aridity in the Mediterranean region will result in longer and recurrent drought. These changes could strongly modify plant defenses, endangering tree survival. We investigate the response of chemical defenses from central and specialized metabolism in Quercus pubescens Willd. to future Mediterranean drought using a long-term drought experiment in natura where trees have been submitted to amplified drought (~ -30% annual precipitation) since April 2012. We focused on leaf metabolites including chlorophylls and carotenoids (central metabolism) and flavonols (specialized metabolism). Measurements were performed in summer from 2016 to 2022. Amplified drought led to higher concentrations of total photosynthetic pigments over the 2016-2022 period. However, it also led to lower AZ/VAZ and flavonol concentrations. Additionally, chemical defenses of Q. pubescens responded to previous precipitation where low precipitation 1 year and/or 2 years preceding sampling was associated to low concentrations of VAZ, flavonol and high neoxanthin concentrations. Our study indicates that the decline of flavonol concentration under long-term drought is counterbalanced by a higher production of several central metabolites. Such results are potentially due to an adjustment in tree metabolism, highlighting the importance of performing long-term experimental studies in natura for assessing drought legacy effects and thus forest adaptation to climate change.