Objective: The objectives of this study were (a) to determine the physical impact of the personal protective equipment (PPE) used in COVID-19 care, specifically the impact on the hydration state of the temperature and the comfort of the healthcare workers who use it, and (b) to show the high-fidelity simulated environment as an appropriate place to test the experimental designs to be developed in real environments for COVID-19. Background: All healthcare staff use full PPE in the care of COVID-19 patients. There are problems, such as excessive sweating, which have not been quantified thus far. Methods: A descriptive pilot design was used in a simulated high-fidelity setting. There was paired activity, with mild–moderate physical activity, between 45 and 60 min continuously, with the COVID-19 PPE. Sixteen intensive care nurses were selected. The before–after differential of weight, thirst, weight use of the PPE, body temperature, thermal body image, general and facial warmth sensation, and perspiration sensation were measured. Results: All subjects lost weight in the form of sweat with both PPEs during the simulation scenario, with a mean of 200 g (0.28% of initial weight), and increased thirst sensation. Body thermal image increased by 0.54 °C in people using the full COVID-19 PPE. Conclusions: The use of PPE in the management of critically ill COVID-19 patients generates weight loss related to excessive sweating. The weight loss shown in this pilot test is far from the clinical limits of dehydration. The use of ventilated PPE, such as PAPR, reduce the body temperature and heat sensation experienced by the users of it; at the same time, it improves the comfort of those who wear it. The simulated environment is a suitable place to develop the piloting of applicable research methodologies in future studies in a real environment.