Developing an ambulatory assist lung (AAL) for patients who need continuous extracorporeal membrane oxygenation has been associated with several design objectives, including the design of compact components, optimization of gas transfer efficiency, and reduced thrombogenicity. In an effort to address thrombogenicity concerns with currently utilized component biomaterials, a low molecular weight water soluble siloxane‐functionalized zwitterionic sulfobetaine (SB‐Si) block copolymer was coated on a full‐scale AAL device set via a one pot aqueous circulation coating. All device parts including hollow fiber bundle, housing, tubing and cannular were successfully coated with increasing atomic compositions of the SB block copolymer and the coated surfaces showed a significant reduction of platelet deposition while gas exchange performance was sustained. However, water solubility of the SB‐Si was unstable, and the coating method, including oxygen plasma pretreatment on the surfaces were considered inconsistent with the objective of developing a simple aqueous coating. Addressing these weaknesses, SB block copolymers were synthesized bearing epoxy or epoxy‐silane groups with improved water solubility (SB‐EP & SB‐EP‐Si) and no requirement for surface pretreatment (SB‐EP‐Si). An SB‐EP‐Si triblock copolymer showed the most robust coating capacity and stability without prior pretreatment to represent a simple aqueous circulation coating on an assembled full‐scale AAL device.