Simultaneous saccharification and fermentation (SSF) of cellulose to ethanol with yeast requires compromising the optimal temperature of T. reesei enzyme (50°C) to allow for microbial growth (30-37°C) of a homoethanol producer. The elimination of organic acids in T. saccharolyticum strain ALK2 allows the operation of an SSF configuration at 50°C without the production of inhibitory salts. This system has been termed thermophilic SSF (tSSF). Thermophilic SSF in turn permits the measurement cellulose hydrolysis rates of T. reesei enzymes at its optimal temperature when the inhibitory hydrolysis products of cellulose are removed via the fermenting organism to the less inhibitory fermentation product ethanol. In this work we measured the degradation of Avicel at 20, 50 and 80 g/L in 1.5L fermentors with T. saccharolyticum ALK2. Ethanol added at the beginning of the tSSF decreased final conversion. Incubation of Spezyme CP in ethanol over time showed an overall decrease in residual enzyme activity as a function of time spent both at 50°C and the ethanol concentration. In addition, a numerical model was developed that fits experimental data at low cellulose concentrations, but deviates as substrate concentration increases. While this work has demonstrated increased activity of T. reesei enzymes at higher temperatures allows a reduction in enzyme requirements, we have also shown an increased in thermo-inactivation as well as inactivation by ethanol at this temperature.