In oenology, bio-protection consists in adding bacteria, yeasts or a mixture of microorganisms on grape must before fermentation in order to reduce the use of chemical compounds such as sulphites. More particularly, non-Saccharomyces yeasts are used as a total or partial alternative to sulphites. However, scientific data capable of proving the effectiveness of adding these yeasts on grape must remain scarce. A single study in white winemaking showed that early addition of a non-Saccharomyces T. del¬brueckii strain could be a microbiological and chemical alternative to sulphites (Simonin et al., 2018). However, there is a lack of scientific data concerning red winemaking where the process allows to leave the yeasts added during the whole winemaking. This study reports for the first time the analysis of microbio¬logical and chemical effects of one Metschnikowia pulcherrima strain, inoculated at the beginning of the red winemaking process in three wineries as an alternative to sulphiting. The implantation of the M. pulcherri¬ma was successful in all the wineries and effectively limited the development of spoilage microorganisms in the same way as the addition of sulphites. The addition of non-Saccharomyces strain could protect must and wine from oxidation as demonstrated by the proanthocyanidin and anthocyanin analysis. Adding M. pulcherrima had no effect on wine volatile compounds and sensorial analysis. However, the un¬targeted analysis by FTICR-MS highlighted a bio-protection signature and an activation of certain metabolic pathways.