Late blight, caused by Phytophthora infestans , is a destructive disease of potato. Defender is the only cultivar in the U.S. with foliar and tuber resistance to this disease. However, this cultivar exhibits susceptibility to infection by Potato virus S (PVS) and severe symptoms appeared on leaves after infection with PVS. PVS is widespread in potato fields in the U.S. To investigate potential interactions between P. infestans and PVS, detached leaves of Defender and Ranger Russet (susceptible to late blight), that were either PVS-infected or non-infected, were inoculated with P. infestans BF-05. The amount of sporulation and the extent of lesion expansion on inoculated leaves were measured to estimate late blight severity. When inoculated with P. infestans only, as expected, Defender exhibited discrete, relatively small, dark purple to black hypersensitive reaction-like spots and on an average had twenty times fewer sporangia compared to Ranger Russet. However, in Defender plants infected with PVS, lesion expansion and sporulation increased significantly compared to PVS-free Defender. The increased severity of late blight in PVS-infected Defender suggests that PVS negatively impacts late blight resistance in this cultivar. This study demonstrates that late blight resistance in cultivars to be released should be screened for PVS susceptibility.