<p>A major requirement for humans is a breathable atmosphere for adequate respiratory CO₂/O₂ gas exchange. In microgravity, despite environmental life support systems regulating air exchange, astronauts complain about air quality, with elevated CO₂-levels resulting in detrimental health and performance effects. Using high-fidelity computational fluid dynamics, we create a model of human respiratory ventilation to show how gravity biophysically shapes and drives respiratory exchange on Earth and in microgravity. On Earth, gravity influences gas exchange through buoyancy and biothermal convection, generating a ‘human thermal body plume’ that drives airflow around the human body, and so facilitates effective gas exchange. We show that the absence of biothermal convection in microgravity reduces this airflow around the human body. This impairs gas exchange by creating an environmental breathing deadspace immediately in front of the face, leading to significant CO₂-rebreathing, with direct implications for astronaut health and countermeasures. This model was also used to estimate engineering requirements for directed external airflow equivalent to that generated by the human thermal body plume to alleviate this problem. Our model further shows that in Earth-normal 1 g, increasing ambient air temperature can also reduce efficient respiratory exchange, resulting in breathing conditions equivalent to those in microgravity, with implications for respiratory health on Earth.</p>