A headspace solid-phase microextraction-gas chromatography-mass spectrometry (HS-SPME/GC-MS) method was used to study the volatile organic compounds (VOCs) associated with the differential immune response of tomato plants infected with the recombinant strain of potato virus Y (PVY^C-to), necrogenic to tomato.  Analysis was carried out in UC82 (UC), a virus susceptible tomato variety, comparing the same UC plants grafted or not onto a virus tolerant tomato ecotype, Manduria (Ma); the three types of samples used for the GC-MS analysis were mock-inoculated UC/Ma plants, UC/Ma+PVY^C-to and UC+PVY^C-to plants; the VOCs obtained were 111.  Results from symptomatic PVY^C-to-infected UC plants showed a VOCs composition enriched in alcohols, fatty acid derivates, benzenoids, and salicylic acid derivatives, while in mock-inoculated UC/Ma plants VOCs were mainly characterized by methyl ester compounds.  The VOC profile was in line with RNAseq data analyses, denoting that PVY^C-to viral RNA accumulation and disease symptoms induce the specific transcriptional activation of genes involved in VOCs biosynthesis.  Furthermore, principal component analysis highlighted that VOCs of PVY^C-to-infected and mock-inoculated grafted plants were much closer each other than that of symptomatic PVY^C-to-infected non-grafted UC plants.  These results suggest that VOCs profiles of tomato plants are related to the viral RNA accumulation, disease intensity and graft-derived tolerance to PVY^C-to infection.