Peach Leaf Curl Disease, caused by the fungus Taphrina deformans, is characterized by reddish hypertrophic and hyperplasic leaf areas. To comprehend the biochemical imbalances caused by the disease an integrated approach including metabolomics, lipidomics, proteomics and complementary biochemical techniques was undertaken. Symptomatic and asymptomatic areas were dissected from leaves with increasing extension of the disease. A differential metabolic behaviour was identified in symptomatic areas with respect to either asymptomatic areas or healthy leaves. Symptomatic areas showed an altered chloroplastic functioning and composition which includes decrease in the photosynthetic machinery, alteration in plastidic lipids, and decreased starch, carotenoid and chlorophyll biosynthesis. In symptomatic areas, decreases in chloroplast redox-homeostasis proteins and in triacylglycerols double bond index were observed. Proteomic data revealed an up-regulation of phenylpropanoid and mevalonate pathways and down-regulation of the plastidic methylerythritol phosphate route. Amino acid pools were affected, with up-regulation of proteins involved in asparagine synthesis. Curled areas exhibited a metabolic shift towards functioning as a sink tissue importing sugars and producing energy through fermentation and respiration and reductive power via the pentose phosphate route. As the disease progresses, reduced asymptomatic areas and healthy leaves diminishes photosynthates production thereby limiting fruit production and ultimately tree survival.