Accurate characterization of polymer-electrolyte fuel cells (PEFCs) requires understanding the impact of mechanical and electrochemical loads on cell components. An essential aspect of this relationship is the effect of compression on the polymer membrane's water-uptake behavior and transport properties. However, there is limited information on the impact of physical constraints on membrane properties. In this paper, we investigate both theoretically and experimentally how the water uptake of Nafion membrane changes under external compression loads. The swelling of a compressed membrane is modeled by modifying the swelling pressure in the polymer backbone which relies on the changes in the microscopic volume of the polymer. The model successfully predicts the water content of the compressed membrane measured through in-situ swelling-compression tests and neutron imaging. The results show that external mechanical loads could reduce the water content and conductivity of the membrane, especially at lower temperatures, higher humidities, and in liquid water. The modeling framework and experimental data provide valuable insight for the swelling and conductivity of constrained and compressed membranes, which are of interest in electrochemical devices such as batteries and fuel cells. (C) 2011 The Electrochemical Society. [DOI: 10.1149/2.097112jes]