Pseudomonas aeruginosa (Pa) is an opportunistic pathogen that threatens the health, especially in immunocompromised individuals. Pseudomonas aeruginosa survives everywhere, including in a shuttle of spaceflights. Survival and starvation of Pa in water probably increase or decrease the degree of pathogenicity or virulence, but it is not well discovered. To promote our understanding of the mechanisms of Pa long-term survival in water, investigations on survival kinetics and its pathogenicity to mice are under investigation in our laboratory. Data has shown that under starvation conditions in water, Pa can lead to (i) survival for over 15 years in water; (ii) distinct changes in colony morphology, including loss of pigmentation. This study also aimed to determine the pathogenicity of clinical and environmental isolates of Pa in water under starved conditions. We hypothesized that the starvation of Pa isolates in water results in different survival curves, morphological, that may enhance pathogenicity in mice. Mice infected with starved isolates showed a lesser death rate than non-starved isolates. This project compared the susceptibility of BALB/c, C57BL/6J, and DBA/2 J in lung infection. Our data shows the vulnerability of DBA/2J was high compared to BALB/c or C57BL/6J. Hindlimb-unloading increased the death rate in DBA/2J compared to BALB/c strains. Lung infection of different Pa isolates shows a differential death rate, with the highest death rate caused by non-starved isolates in mice. Overall, long-term starvation of Pa isolates exits may lead to a reduced mortality rate of mice.