Xylella fastidiosa is an insect vector-transmitted bacterial plant pathogen associated with severe diseases in a wide range of plants. In last decades, X. fastidiosa was detected in several European countries. Among X. fastidiosa subspecies, here we study X. fastidiosa subsp. pauca associated with the Olive Quick Decline Syndrome (OQDS) causing severe losses in Southern Italy. First, we collected Olea europaea L. (cv. Ogliarola salentina) samples in groves located in infected zones and uninfected zones. Secondly, the untargeted LC-TOF analysis of the lipid profiles of OQDS positive (+) and negative (-) plants showed a significant clustering of OQDS+ samples apart from OQDS- ones. Thirdly, using HPLC-MS/MS targeted methods and chemometric analysis, we identified a shortlist of 10 lipids significantly different in the infected versus healthy samples. Last, we observed a clear impact on X. fastidiosa subsp. pauca growth and biofilm formation in vitro liquid cultures supplemented with these compounds. Considering that growth and biofilm formation are primary ways by which X. fastidiosa causes disease, our results demonstrate that lipids produced as part of the plant's immune response can exacerbate the disease. This is reminiscent of an allergic reaction in animal systems, offering the depression of plant immune response as a potential strategy for OQDS treatment