Climate change in the Mediterranean area is making summers warmer and dryer. Grapevine (Vitis vinifera L.) is mostly important for wine production in Mediterranean countries, and the variety Tempranillo is one of the most cultivated in Spain and Portugal. Drought decreases yield and quality and causes important economic losses. As full irrigation has negative effects on quality and water is scarce in this region, deficit irrigation is often applied. In this research, we studied the effects of two deficit irrigation treatments, Sustained Deficit Irrigation (SDI) and Regulated Deficit Irrigation (RDI), on the transcriptome of grape berries at full maturation, through RNAseq. The expression of differentially regulated genes (DEGs) was also monitored through RT-qPCR along berry development. Most transcripts were regulated by water stress, with a similar distribution of up- and down-regulated transcripts within functional categories (FC). Primary metabolism was the more severely affected FC under water stress, followed by signaling and transport. Almost all DEGs monitored were significantly up-regulated by severe water stress at veraison. The modulation of an auxin response repression factor, AUX22D, by water stress indicates a role of this gene in the response to drought. Further, the expression of WRKY40, a TF that regulates anthocyanin biosynthesis, may be responsible for changes in grape quality under severe water stress.