AbstractBackground:Fermentation completion is a major prerequisite in many industrial processes involving the bakeryyeastSaccharomyces cerevisiae.Stuck fermentations can be due to the combination of many environmental stresses.Among them, high temperature and ethanol content are particularly deleterious especially in bioethanol and redwine production. Although the genetic causes of temperature and/or ethanol tolerance were widely investigated inlaboratory conditions, few studies investigated natural genetic variations related to stuck fermentations in highgravity matrixes.Results:In this study, three QTLs linked to stuck fermentation in winemaking conditions were identified by using aselective genotyping strategy carried out on a backcrossed population. The precision of mapping allows theidentification of two causative genesVHS1andOYE2characterized by stop-codon insertion. The phenotypic effectof these allelic variations was validated by Reciprocal Hemyzygous Assay in high gravity fermentations (> 240 g/L ofsugar) carried out at high temperatures (> 28 °C). Phenotypes impacted were mostly related to the late stage ofalcoholic fermentation during the stationary growth phase of yeast.Conclusions:Our findings illustrate the complex genetic determinism of stuck fermentation and open newavenues for better understanding yeast resistance mechanisms involved in high gravity fermentations.