Miniature high-performance micro fuel cells (μFC) operating at room temperature have been fabricated using microsystems technologies. The smallest μFCs have a reaction surface of 0.11 cm2 (volume ∼18.6 mm3; mass ∼35.6 mg) and produce an output power density of 22.9 mW/cm2. The insertion of a hydrophilic macroporous layer into the anode diffusion layer stack, an input fuel flow rate as low as 550 nL min−1 produces 9.25 mW/cm2 at a fuel use efficiency of ∼75%. By optimizing the microfluidic architecture, e.g. the microchannel dimensions and the diffusion layer stack, we demonstrate of the smallest, highest performance μFCs reported to date