The majority of astronauts suffer immune dysfunction, as evident by latent virus reactivation and hypersensitivity reactions. This pilot study aims to demonstrate the feasibility of using a systems biology-based proteomics approach, including a commercial platform (Oncohost), to decipher the complexity of spaceflight-induced immune dysfunction. We will describe immune dysfunction pathophysiology that can be applied to both human diseases, and to the physiological responses seen when the body is exposed to extreme conditions. Such work will facilitate the stratification of immune dysfunction into appropriate molecular subtypes and facilitate the development of personalized therapies and interventions aiming to preserve / restore immune function.