The plasma membrane Na+/H+-antiporter salt overly sensitive1 (SOS1) from the halophytic Arabidopsis-relative Thellunglella halophila (ThSOS1) shows conserved sequence and domain structure with the orthologous genes from Arabidopsis thaliana and other plants. When expression of ThSOS1 was reduced by RNA interference (RNAi), pronounced characteristics of salt-sensitivity were observed. We were interested in monitoring altered transcriptional responses between Thellungiella wild type and thsos1-4, a representative RNAI line with particular emphasis on root responses to salt stress at 350 mmol/L NaCl, a concentration that is only moderately stressful for mature wild type plants. Transcript profiling revealed several functional categories of genes that were differently affected in wild-type and RNAi plants. Down-regulation of SOS1 resulted In different gene expression even In the absence of stress. The pattern of gene induction in the RNAi plant under salt stress was similar to that of glycophytic Arabidopsis rather than that of wild type Thellungiella. The RNAi plants failed to down-regulate functions that are normally reduced in wild type Thellungiella upon stress and did not up-regulate functions that characterize the Thellungiella salt stress response. Metabolite changes observed in wild type Thellungiella after salt stress were less pronounced or absent in RNAi plants. Transcript and metabolite behavior suggested SOS1 functions including but also extending its established function as a sodium transporter. The down-regulation of ThSOS1 converted the halophyte Thellungiella into a salt-sensitive plant.