Real time knowledge of the metabolic workload of an astronaut during an Extra-Vehicular Activity (EVA) can be instrumental for space suit research, design, and operation. Three indirect calorimetry approaches were developed to determine the metabolic workload of a subject in an open-loop space suit analogue. A study was conducted to compare the data obtained from three sensors: oxygen, carbon dioxide, and heart rate. Subjects performed treadmill exercise in an enclosed helmet assembly, which simulated the contained environment of a space suit while retaining arm and leg mobility. These results were validated against a standard system used by exercise physiologists. The carbon dioxide sensor method was shown to be the most reliable and a calibrated version of it is recommended for implementation into the MX-2 neutral buoyancy space suit analogue.