Human exploration of space, facilitated by electrochemical systems, will require integration of many seemingly disparate systems including but not limited to power systems, in situ resource utilization (ISRU), and environmental control and life support (ECLS). Through combining expressions of the First and Second Laws of Thermodynamics exergy quantifies the useful work that can be obtained from a system, subject to environmental limitations. This approach provides a means of integrating diverse systems and components based on one consistent and physically meaningful property: exergy. Using this property as a basis, diverse systems can be analyzed and integrated effectively based on the exergy destruction and exergy efficiency. Here, the applicability of exergy analysis to systems design and integration is demonstrated through two examples involving electrochemical systems that support human space exploration.First, analysis of the ECLS system aboard the International Space Station (ISS) is conducted to assess its overall performance in terms of exergy destruction rates and exergy efficiency. The ECLS system is divided into constituent subsystems which are further divided into key components. Based on this system decomposition, exergy balances are derived for each component and subsystem. Special focus is given to the Oxygen Generation Assembly (OGA) within the ECLS Atmospheric Revitalization Subsystem. The results of parametric studies of the OGA proton exchange membrane electrolyzer performance are presented with an emphasis on the impacts of operational conditions on exergy efficiency. This electrolyzer is a significant contributor to system exergy destruction and exhibits a low exergetic efficiency. It therefore presents an opportunity for improving overall ECLS system performance.Following the example of ECLS exergy analysis, the application of exergy analysis to the integration of power and ISRU systems for lunar exploration is presented through system level models. Exergy destruction and efficiency are quantified over the lunar diurnal cycle for power and ISRU systems. The power systems analysis focuses on photovoltaic arrays paired with battery and regenerative fuel cell systems. The ISRU system analysis focuses on production of oxygen from lunar regolith through the reduction of ilmenite combined with water electrolysis. Here the application of exergy analysis identifies key opportunities for the use of byproduct heat and the optimal sizing of system components.The studies presented demonstrate the capability of exergy analysis to support the design and integration of electrochemical systems within larger power, ISRU, and ECLS systems supporting space exploration. This approach can enable the full and efficient use of a system’s available work potential based on a consistent, physically meaningful property. Therefore, exergy analysis is shown to be a key tool for the future design and integration of electrochemical systems for space exploration.