Fusarium virguliforme causes the most damaging fungal disease of soybean sudden death syndrome (SDS). Host resistance requires the resistance allele at Rfs2. Resistance protects the the plant’s roots by about 24-48 h after infestation. In addition, 4-8 days later a systemic acquired resistance (SAR) develops that discourages later infections. The molecular mechanisms that control the resistance response were complex, as judged by transcript abundance changes, in near isogeneic lines (NILs) and transgenic plants. This study aimed to focus on key post-transcriptional changes by identifying proteins and metabolites that were increased in abundance in both resistant and susceptible NILs and transgenic plants with Rfs2 at new genomic locations. Comparisons were made among NILs and transgenic plants 10 days after SCN infestation and without SCN infestation. Two dimensional gel electrophoresis resolved more than 1,000 protein spots on each gel. Only twenty two protein spots with a significant (P<0.05) difference in abundance of 1.5 fold or more were found among the four treatments and a pair of NILs. There were 30 differences among transgenic plant pair of genotypes. The proteins were grouped into six functional categories; stress response; disease response; transcriptional regulation; protein degradation; intracellular trafficking; and cell wall metabolism. Metabolite analysis by GC-MS identified 28 were changes in primary metabolisms and twenty two in secondary metabolisms . Pathways altered were associated with SAR-like responses wheras jasmonate signaling was inhibited or reduced. The pathways impacted focused on a smaller set of key proteins that may form the basis of new assay for the selection of resistance to SDS in soybean.