Sclerotinia stem rot [caused by Sclerotinia sclerotiorum (Lib.) de Bary] is considered the second most important cause of yield loss in soybean [Glycine max (L.) Merr]. Soybean cultivars show variability in susceptibility, but no complete resistance to the disease has been reported and little information on the genetics of resistance is available. The objective of this study was to identify putative quantitative trait loci (QTLs) associated with Sclerotinia stem rot resistance in soybean. Recombinant inbred lines (RILs) from five populations were developed by crossing Williams 82, a susceptible cultivar, with five cultivars exhibiting partial resistance: Corsoy 79, Dassel, DSR173, S19-90, and Vinton 81. The F2 to F5 generations were advanced by single seed descent. Parental polymorphism was tested with 507 simple sequence repeat (SSR) primers from the integrated linkage map of soybean, and primers were selected for progeny screening in the five populations on the basis of polymorphism and distribution in the genome. Five hundred RILs, consisting of 100 F5:6 lines from each population, were evaluated for resistance to Sclerotinia sclerotiorum isolate 143 by a detached leaf method in the laboratory to measure lesion area on leaves inoculated with mycelium plugs. Single degree of-freedom contrasts in PROC MIXED and interval analysis were used to detect putative QTLs. Twenty-eight putative QTLs for resistance to Sclerotinia stem rot of soybeans were identified on 15 different linkage groups in five RIL populations by single degree-of-freedom contrasts. Alleles involved in reduction of lesion size came from both the resistant and susceptible parents, and transgressive segregates were identified in two populations. The amount of phenotypic variation explained by individual QTLs ranged from 4 to 10%. Seven QTLs on seven different linkage groups were identified in multiple populations with some QTL regions corresponding with mapped resistance genes and resistance gene analogs. The results suggest that several genes control resistance to Sclerotinia stem rot and that markers could facilitate an initial screen of segregating breeding populations.