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The continuing development of avionics for Unmanned Aircraft Systems (UASs) is introducing higher levels of intelligence and autonomy both in the flight vehicle and in the ground mission control, allowing new promising operational concepts to emerge. One-to-Many (OTM) UAS operations is one such concept and its implementation will require significant advances in several areas, particularly in the field of Human–Machine Interfaces and Interactions (HMI²). Measuring cognitive load during OTM operations, in particular Mental Workload (MWL), is desirable as it can relieve some of the negative effects of increased automation by providing the ability to dynamically optimize avionics HMI² to achieve an optimal sharing of tasks between the autonomous flight vehicles and the human operator. The novel Cognitive Human Machine System (CHMS) proposed in this paper is a Cyber-Physical Human (CPH) system that exploits the recent technological developments of affordable physiological sensors. This system focuses on physiological sensing and Artificial Intelligence (AI) techniques that can support a dynamic adaptation of the HMI² in response to the operators’ cognitive state (including MWL), external/environmental conditions and mission success criteria. However, significant research gaps still exist, one of which relates to a universally valid method for determining MWL that can be applied to UAS operational scenarios. As such, in this paper we present results from a study on measuring MWL on five participants in an OTM UAS wildfire detection scenario, using Electroencephalogram (EEG) and eye tracking measurements. These …