Cellobiose dehydrogenase catalyzes the oxidation of various carbohydrates and is considered as a possible anode catalyst in biofuel cells. It has been shown that the catalytic performance of this enzyme immobilized on electrodes can be increased by presence of calcium ions. To get insight into the Ca²⁺-induced changes in the immobilized enzyme we employ surface-enhanced vibrational (SERR and SEIRA) spectroscopy together with electrochemistry. Upon addition of Ca²⁺ ions electrochemical measurements show a shift of the catalytic turnover signal to more negative potentials while SERR measurements reveal an offset between the potential of heme reduction and catalytic current. Comparing SERR and SEIRA data we propose that binding of Ca²⁺ to the heme induces protein reorientation in a way that the electron transfer pathway of the catalytic FAD center to the electrode can bypass the heme cofactor, resulting in catalytic activity at more negative potentials. A new road: Electrochemistry combined with surface enhanced vibrational (SERR and SEIRA) spectroscopy are employed to obtain mechanistic insight into the catalytic performance of cellobiose dehydrodegane (MtCDH) immobilized on noble metal electrodes in the presence of Ca²⁺ ions. The results show induced reorientation of the enzyme on the electrode, which leads to a new electron transfer pathway between the protein and the electrode.