The first step in the Phosphorylated Pathway of serine (Ser) Biosynthesis (PPSB) is catalyzed by the enzyme Phosphoglycerate Dehydrogenase (PGDH), coded in Arabidopsis thaliana by three genes. Gene expression analysis indicated that PGDH1 and PGDH2 were induced, while PGDH3 was repressed, by salt-stress. Accordingly, PGDH3 overexpressing plants (Oex PGDH3) were more sensitive to salinity than wild type plants (WT), while plants overexpressing PGDH1 (Oex PGDH1) performed better than WT under salinity conditions. Oex PGDH1 lines displayed lower levels of the salt-stress markers proline and raffinose in roots than WT under salt-stress conditions. Besides, the ratio of oxidized glutathione (GSSG) without and with salt-stress was the highest in Oex PGDH1, and the lowest in Oex PGDH3 compared to WT. These results corroborated that PGDH3 activity could be detrimental, while PGDH1 activity could be beneficial for plant salt tolerance. Under salt-stress conditions, PGDH1 overexpression increased Ser content only in roots, while PGDH3 overexpression increased the amino acid level in both aerial parts and roots, compared to the WT. Our results indicate that the response of PGDH family genes to salt-stress depends on the specific gene studied and that increases in Ser content are not always correlated with enhanced plant salt tolerance. Copyright © 2019 Elsevier B.V. All rights reserved.