Sudden death syndrome (SDS) caused by the ascomycete fungus, Fusarium virguliforme, is one of the top four yield reducing diseases in soybean. The pathogen causes both root necrosis and foliar SDS. However, the pathogen has never been detected in the diseased foliar tissues. Foliar SDS is believed to be caused by host selective toxins, including FvTox1, secreted by the fungus. We investigated if the xylem sap of F. virguliforme-infected soybean seedlings contains secreted F. virguliforme-peptides, which could be involved in foliar SDS development. We applied LC-MS/MS in analyzing the proteomes of the xylem saps collected from either healthy or F. virguliforme-infected soybean seedlings and identified seven F. virguliforme peptides with secretion signal peptides. The same seven peptides were also identified from the F. virguliforme culture filtrate that causes foliar SDS, when fed to cut soybean seedlings. One of these peptides showed high sequence identity to cereto-platanin, a phytotoxin produced by Ceratocystis fimbriata f. sp. platani that causes canker stain disease in the plane tree. Of the 135 soybean proteins identified, 14 were unique to the xylem sap of the F. virguliforme-infected soybean seedlings and 16 were to the sap of healthy seedlings. This study suggested that multiple F. virguliforme proteins could be involved in foliar SDS development. Furthermore, a number of soybean sap proteins could be differentially accumulated in the infected soybean seedlings in response to F. virguliforme infection. This proteomic study revealed several peptides whose roles in the soybean-F. virguliforme interaction could be crucial in developing foliar SDS.