The label-free shotgun proteomics analysis carried out in this study aimed to understand the molecular mechanisms that contribute towards tomato susceptibility to Xanthomonas euvesicatoria pv. perforans (Xep). To achieve this, comparative proteomics was performed on susceptible inoculated plants with the bacterium and the control group (saline solution) at 24 and 48 h after inoculation (hai). The results revealed that most of the identified proteins showed increased abundance in the infected group and were classified into different gene ontology groups. Eight of these proteins were related to susceptibility in other pathosystems, suggesting their potential involvement in the development of bacterial spot in tomato. Some of these proteins are involved in the negative regulation of salicylic acid, PR proteins and reactive oxygen species (ROS), as well as contributing to the acquisition of sugars by the pathogen. The results obtained in this study provided us with valuable information for understanding the molecular mechanisms that lead to tomato susceptibility to Xep and will help in developing tomato cultivars resistant to bacterial spot. SIGNIFICANCE: Our proteomic study of tomato plants during infection by Xep allowed for the identification of potential proteins that contribute to bacterial spot tomato disease development. These proteins can act in different ways to favor the pathogen, such as the negative modulation of phytohormones involved in plant defense, the inhibition of PR proteins and reactive oxygen species, as well as to collaborate in the acquisition of sugar for pathogen nutrition.