Caenorhabditis(C.)eleganshas become a popular toxicological and biological test organism in the last two decades. Furthermore, the role ofC. elegansas an alternative for replacing or reducing animal experiments is continuously discussed and investigated. In the current study, we investigated whetherC. eleganssurvival assays can help in determining differences in the virulence ofSalmonella entericastrains and to what extentC. elegansassays could replace animal experiments for this purpose. We focused on three currently discussed examples where we compared the longevity ofC. eleganswhen fed (i) withS.entericaserovar Enteritidis vaccination or wild-type strains, (ii) with lipopolysaccharide (LPS) deficient rough or LPS forming smoothS.entericaserovar Enteritidis, and (iii) with anS. entericasubsp.diarizonaestrain in the presence or absence of the typical pSASd plasmid encoding a bundle of putative virulence factors. We found that theC. eleganssurvival assay could indicate differences in the longevity ofC. eleganswhen fed with the compared strain pairs to a certain extent. Putatively higher virulentS. entericastrains reduced the lifespan ofC. elegansto a greater extent than putatively less virulent strains. TheC. eleganssurvival assay is an effective and relatively easy method for classifying the virulence of different bacterial isolatesin vivo, but it has some limitations. The assay cannot replace animal experiments designed to determine differences in the virulence ofSalmonella entericastrains. Instead, we recommend using the described method for pre-screening bacterial strains of interest to select the most promising candidates for further animal experiments. TheC. elegansassay possesses the potential to reduce the number of animal experiments. Further development of theC. elegansassay in conjunction with omics technologies, such as transcriptomics, could refine results relating to the estimation of the virulent potential of test organisms.