This study investigated the effects of spaceflight and simulated microgravity on the virulence of *Serratia marcescens* using *Drosophila melanogaster* as a model host. *S. marcescens* grown on the International Space Station (ISS) exhibited significantly increased lethality to *D. melanogaster* compared to ground controls. This increased virulence was reversible after ground passaging. Simulated microgravity conditions using a rotating wall vessel also resulted in increased virulence. The increased virulence was observed in both wild-type flies and immune pathway mutants, suggesting that changes in host immunity are not the primary factor. Space-flown bacteria showed increased growth rates both in vitro and in vivo. The results highlight complex physiological changes in bacteria in space environments.
