AbstractThe electrochemical regeneration of the reduced form of nicotinamide adenine dinucleotide cofactor (NADH) was realized in a hybrid flow reactor coupling fuel cell technology and redox flow device, paying attention to the robust immobilization of all catalysts. The rhodium catalyst Rh(Cp✶)(bpy)Cl+ was covalently immobilized on a multi‐walled carbon nanotube (MWCNT) layer and the association with the gas diffusion electrode was carefully optimized. High stability and activity of the electrochemical system were assessed by cyclic voltammetry and amperometry in the flow reactor. Afterwards, the optimal cofactor regeneration was applied to NADH‐dependent biosynthesis using immobilized lactate dehydrogenase for the conversion of pyruvate to lactate in the flow cell in the presence of cofactor concentration as low as 10 μM. 79 % Faradaic efficiency was achieved and remarkable total turnover number (TTN) were reached: 2500, 18000, and 180000, for NADH, Rh complex and L‐lactate dehydrogenase (LDH), respectively.