Nanostructured membranes with precisely engineered nanopores were fabricated on a thin silicon nitride membrane, using a combination of bulk micromachining and focused-ion-beam drilling. These membranes are designed to preserve microscale blood channel dimensions, thereby permitting the red cell shape change that enhances gas exchange in the pulmonary capillary. The membranes were tested for their mechanical stability and the results were verified with finite element analysis. Initial studies have proven the membranes to be robust, and capable of withstanding pressures typically experienced in blood oxygenator channels. A novel MEMS-based blood oxygenation system employing the nanoporous membranes is also presented. The oxygenation system is designed to have controlled blood and gas volumes for efficient blood oxygenation. © 2008 IEEE.