AbstractA response surface methodology with 2k full factorial design was applied to obtain optimum conditions for bioethanol production using coffee mucilage (CM) as the substrate and Saccharomyces cerevisiae NRRL Y-2034 as the inoculum. CM is an agro-industrial residue mainly composed of simple sugars; the product yield and productivity process were analyzed with respect to the fermentation, pH, temperature, and the initial sugar concentration. Employing the following predicted optimum operational conditions attained the highest bioethanol production: pH 5.1, temperature 32 °C, and initial sugar concentration 61.8 g/L. The estimated bioethanol production was 15.02 g/L, and the experimental production was 16.29 g/L ± 0.39 g/L, with a bioethanol yield of 0.27 g/L and a productivity process of 0.34 g/Lh. Glycerol was the predominant byproduct of the fermentative metabolism of S. cerevisiae. The response surface methodology was successfully employed to optimize CM fermentation. In the fermentative processes with yeast, optimizing the conditions of the culture medium is needed to fully exploit the potential of the strains and maximize the production of bioethanol.