Eliminating the expensive and failure-prone proton exchange membrane (PEM) together with the platinum-based anode and cathode catalysts would significantly reduce the high capital and operating costs of low-temperature (<373 K) fuel cells. We recently introduced the Swiss-roll mixed-reactant fuel cell (SR-MRFC) concept for borohydride–oxygen alkaline fuel cells. We now present advances in anode electrocatalysis for borohydride electrooxidation through the development of osmium nanoparticulate catalysts supported on porous monolithic carbon fiber materials (referred to as an osmium 3D anode). The borohydride–oxygen SR-MRFC operates at 323 K and near atmospheric pressure, generating a peak power density of 1880 W m−2 in a single-cell configuration by using an osmium-based anode (with an osmium loading of 0.32 mg cm−2) and a manganese dioxide gas-diffusion cathode. To the best of our knowledge, 1880 W m−2 is the highest power density ever reported for a mixed-reactant fuel cell operating under similar conditions. Furthermore, the performance matches the highest reported power densities for conventional dual chamber PEM direct borohydride fuel cells.