Context and purpose of the study – The use of new fungus disease-tolerant grapevine varieties is a long-term and promising solution to reduce chemical input in viticulture. However, little is known about the effects of water deficit (WD) on the thiol aromatic potential of new varieties coming up from breeding programs. Varietal thiols such as 3-sulfanylhexan-ol (3SH), 4-methyl-4-sulfanylpentan-2-one (4MSP) and their derivatives are powerful aromatic compounds present in wines coming from odorless precursors in grapes, and could contribute to the wine typicity of such varieties. This study aimed to characterize the fruit response of 6 new INRAE fungus disease-tolerant varieties and the Syrah control in (i) thiol precursor levels and (ii) main primary metabolites accumulation. Material and methods – Field grown vines of 3 white (Floréal, 3159B and G5) and 3 red (Artaban, 3176N and G14) fungus disease-tolerant varieties and Syrah were individually monitored during the 2021 season. A gradient of WD was applied and followed by weekly measures of predawn water potentials. Grapes were sampled at the physiological ripe stage (phloem unloading arrest into berries). Primary metabolites (glucose, fructose, tartrate, malate and yeast assimilable nitrogen) were assessed by HPLC and enzymatic methods. Thiol precursors as S-conjugate to glutathione (G3SH and G4MSP), to cysteine (Cys3SH and Cys4MSP) and to dipeptides (CysGly3SH and g-GluCys3SH) were analyzed by LC-MS/MS using Stable Isotope Dilution Assay quantification approach. Results – Despite genotypes showing low differences on primary metabolites concentrations, a great variability on thiol precursors levels was reported. Among all precursors only G3SH, Cys3SH and CysGly3SH were identified and quantified in all genotypes. For all genotypes, G3SH contents accounted for 75% – 100% of the thiol aromatic potential, while Cys3SH and CysGly3SH accounted for a maximum of 16% and 13%, respectively. Regardless of WD level, the concentrations of G3SH ranged from 31 µg/kg to 132 µg/kg in white varieties (G5 and Floréal respectively) and from 68 µg/kg to 466 µg/kg in red varieties (Syrah and 3176N respectively). Minor effects of WD were observed on soluble sugars, organic acids, YAN and thiol precursor concentrations expressed as µg/kg (average concentrations). However, severe WD strongly reduced all metabolites production per unit of fruit and per plant. The most impacted genotype by severe WD was Floréal, which showed reductions of 70% in primary metabolites and thiol precursors quantity per plant. The least impacted genotype regarding primary metabolites quantity per plant was 3176N (-20%) while Artaban showed the lowest reductions in thiol precursors per plant (-25%). These results showed that a severe WD ultimately reduce the production of metabolites per unit area of cultivation or plant without significantly improving the concentration of compounds of interest in the grape, potentially causing significant economic losses.