Sclerotinia stem rot is an important soybean disease. An increase in phytoalexin production with herbicide treatments may reduce the incidence of this disease in soybean. Research was conducted to determine soybean response, Sclerotinia sclerotiorum lesion development, and phytoalexin production in glyphosate-resistant and -susceptible soybean cultivars treated with protoporphyrinogen oxidase–inhibiting herbicides. Necrosis of soybean leaves 7 d after postemergence application of oxyfluorfen at 17.5 g ai/ha, carfentrazone at 1.8 g ai/ha, sulfentrazone at 9.0 g ai/ha, fomesafen at 280 g ai/ha, acifluorfen at 425 g ai/ha, flumiclorac at 30 g ai/ha, CGA-248757 at 4 g ai/ha, and oxadiazon at 280 g ai/ha was equal to or less than lactofen at 70 g ai/ha. In a detached leaf bioassay, S. sclerotiorum lesion diameter was reduced by oxyfluorfen, carfentrazone, sulfentrazone, lactofen, fomesafen, flumiclorac, and oxadiazon compared with the untreated control. Furthermore, lesion diameter on untreated leaves of soybean treated with oxyfluorfen, carfentrazone, sulfentrazone, lactofen, fomesafen, acifluorfen, flumiclorac, CGA-248757, and oxadiazon was reduced compared with the untreated control. Lactofen and sulfentrazone increased leaf phytoalexin production similarly, but neither herbicide affected stem phytoalexin production compared with the untreated control. Glyphosate-resistant and near-isogenic–susceptible cultivars responded similarly when inoculated with S. sclerotiorum in the detached leaf bioassay. Glyphosate-resistant S20-B9 and P93B01 produced more phytoalexins than glyphosate-susceptible S 19-90 and P9281. Herbicide treatments may increase phytoalexin production in leaves of treated plants, but levels in the stem do not explain protection from Sclerotinia stem rot.