Coral reefs are under increasing stress caused by global and local environmental changes, which are thought to increase the susceptibility of corals to opportunistic pathogens. In the absence of an easily culturable model animal, the understanding of the mechanisms of disease progression in corals remains fairly limited. In the present study, we tested the susceptibility of the tropical sea anemoneAiptasia pallidato an opportunistic coral pathogen (Serratia marcescens).A. pallidawas susceptible toS. marcescensPDL100 and responded to this opportunistic coral pathogen with darkening of the tissues and retraction of tentacles, followed by complete disintegration of polyp tissues. Histological observations revealed loss of zooxanthellae and structural changes in eosinophilic granular cells in response to pathogen infection. A screen ofS. marcescensmutants identified a motility and tetrathionate reductase mutants as defective in virulence in theA. pallidainfection model. In co-infections with the wild-type strain, the tetrathionate reductase mutant was less fit within the surface mucopolysaccharide layer of the host coralAcropora palmata.