The complement system plays an important role in inflammation, innate and acquired immunity, as well as homeostasis. Despite these functions, the effects of spaceflight conditions on the complement system have not yet been intensively studied. Consequently, we investigated the effects of five types of chronic stressors, similar to those encountered during a stay onboard the International Space Station, on C3 expression in larvae of the urodele amphibian Pleurodeles waltl. We focused on C3 because it is a critical component of this system. These studies were completed by the analysis of adult mice exposed to two models of inflight stressors. Our data show that simulating space radiation, or combining a modification of the circadian rhythm with simulated microgravity, affects the amount of C3 proteins. These results suggest that C3 expression could be modified under real spaceflight conditions, potentially increasing the risk of inflammation and associated tissue damage.