<p>Major bottleneck present in the scalability of enzymatic glucose fuel cells (EGFCs) is the complex interdependency of various factors such as mass transport, reaction kinetics and electron transfer mechanisms leading to loss in performance. Mathematical modeling using dimensionless quantities is crucial as it aids in quantifying the various losses present in EGFCs. A model is developed using Damkohler number (<i>Da</i>) to study the substrate transport – reaction interactions considering the deactivation of enzymes in mediated EGFCs. The variation of <i>Da</i> with operating parameters such as substrate and enzyme concentration, length and porosity of the electrode, and operating temperature is modeled. Modeling results indicate that initially <i>Da</i> increases with substrate concentration. However beyond a certain substrate concentration, the <i>Da</i> is found to decrease. <i>Da</i> is found to increase with increasing enzyme concentration, electrode porosity and length. The performance of EGFCs is evaluated using the variation in electrode overpotential and current density. The model is found to be compliant with the literature data.</p>