The rational design of methodologies to control the neoformed compounds occurrence (NFCs), such as acrylamide and hydroxymethylfurfural (HMF) in roasted coffee, must consider the preservation of the bioactive compounds contained in this beverage. The aim of this work was to evaluate the integrated effect of yeast inoculation during the fermentation stage and the modification of roasting parameters on the final concentrations of NFCs and bioactive compounds of roasted coffee. A completely randomized factorial design was used to evaluate the effect of yeast inoculation (with and without inoculation), roasting temperature (150, 180 and 210 °C) and roast degree (medium, dark) on the (i) physicochemical characteristics (volume change, mass loss, water activity, non-enzymatic browning index, antioxidant capacity, total polyphenols, chlorogenic acid and caffeine) as well as HMF and acrylamide levels of roasted coffee. Response variables were analyzed separately by ANOVA and clustering of treatments was explored by PCA. Yeast inoculation did not significantly (p > 0.05) affect volume change, mass loss, antioxidant capacity, total polyphenols content, and caffeine contents. The interaction of evaluated factors significantly decreased (p < 0.05) the acrylamide and HMF contents of roasted coffee (43 % and 56.0 %, respectively). Based on PCA grouping the best treatments were medium roast at 210 °C (inoculated and uninoculated) and at 180 °C (inoculated). Under these conditions it is possible to produce a roasted coffee mitigated in neo formed contaminants that present the physicochemical properties of original product.