Carbon Dioxide as a Multisystem Threat in Long Duration Spaceflight

Elevated partial pressure of carbon dioxide (Pco2) poses a persistent health challenge during spaceflight. Unlike Earth's environment, the International Space Station experiences Pco2 levels that often exceed terrestrial safety thresholds, creating unique physiological risks for astronauts. In microgravity, localized Pco2 "pockets" can form due to lack of convection, exacerbating hypercapnic symptoms such as headaches, visual disturbances, and cognitive impairments. Moreover, microgravity-induced cephalad fluid shifts amplify the impact of CO2-mediated cerebral vasodilation, contributing to elevated intracranial pressure and potentially exacerbating spaceflight-associated neuro-ocular syndrome. Chronic hypercapnia also raises concerns about bone demineralization and renal stone formation, compounding mission risks. As we move toward longer missions to the Moon and Mars, mitigating CO2-related health effects through engineering controls, physiological countermeasures, and enhanced monitoring is essential. This article discusses current evidence and calls for integrated strategies to safeguard astronaut health and mission success under the compounded stressors of CO2 exposure and microgravity. Evans LA. Carbon dioxide as a multisystem threat in long duration spaceflight. Aerosp Med Hum Perform. 2025; 96(11):1024-1026.