Xylella fastidiosa subsp. pauca (Xfp), strain CoDiRO, infects a broad range of olive (Olea europaea L.) cultivars. The profile of phenolic compounds, progression of leaf scorch symptoms and population density of X. fastidiosa were analyzed in response to Xfp infection, in four olive cultivars (Cellina di Nardo Ogliarola di Lecce, Frantoio and Leccino). Differences in X. fastidiosa multiplication in xylem tissues were estimated using qPCR assays, showing that cvs. Cellina di Nardoand Ogliarola di Lecce were characterized by fewer threshold cycles than for cvs. Frantoio and Leccino. Periodical visual inspections of symptomatic plants estimated disease severity and progression using a disease rating scale; cvs. Frantoio and Leccino showed some disease resistance with up to 3-fold severity scores than those for cvs. Cellina di Nardoand Ogliarola. During vegetative growth, Xfp-positive leaf samples were analyzed using HPLC-ESI-TOF-MS. Among quantified phenolic compounds, Xfp infection modified hydroxytyrosol glucoside and quinic acid. Constitutive levels of hydroxytyrosol glucoside were greater in cvs. Frantoio and Leccino compared to Cellina di Nardoand Ogliarola di Lecce, while levels were strongly reduced in infected plants (95% reduction in Cellina di Nardo 94% in Ogliarola di Lecce, 97% in Frantoio and 98% in, Leccino). Constitutive levels of quinic acid did not differ among cultivars, but strongly increased in infected Cellina di Nardoand Ogliarola di Lecce (5-fold increases), and to a lesser extent (4-fold increases) in infected Frantoio and Leccino. These results were consistent with the previously reported positive association of quinic acid with X. fastidiosa subsp. fastidiosa symptoms and titres in grapevine. Differences in the induced responses of these phenolic compounds among cultivars suggest that they play defensive roles in olive tree response to X. fastidiosa infection.