Extracorporeal membrane oxygenation (ECMO) is a life support system that circulates the blood through an oxygenating system to temporarily (days to months) support heart or lung function during cardiopulmonary failure until organ recovery or replacement. Currently, the need for high levels of systemic anticoagulation and the risk for bleeding are main drawbacks of ECMO that can be addressed with a redesigned ECMO system. Our lab has developed an approach using microelectromechanical systems (MEMS) fabrication techniques to create novel gas exchange membranes consisting of a rigid silicon micropore membrane (SμM) support structure bonded to a thin film of gas‐permeable polydimethylsiloxane (PDMS). This study details the fabrication process to create silicon membranes with highly uniform micropores that have a high level of pattern fidelity. The oxygen transport across these membranes was tested in a simple water‐based bench‐top set‐up as well in a porcine in vivo model. It was determined that the mass transfer coefficient for the system using SµM‐PDMS membranes was 3.03 ± 0.42 mL O2 min−1 m−2 cm Hg−1 with pure water and 1.71 ± 1.03 mL O2 min−1 m−2 cm Hg−1 with blood. An analytic model to predict gas transport was developed using data from the bench‐top experiments and validated with in vivo testing. This was a proof of concept study showing adequate oxygen transport across a parallel plate SµM‐PDMS membrane when used as a membrane oxygenator. This work establishes the tools and the equipoise to develop future generations of silicon micropore membrane oxygenators.