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Salmonella Typhimurium encounters several stress, including oxidants generated by the phagocytes and higher (42 °C) body temperature inside the poultry host.To withstand such assaults, three types of energy dependant proteases, including the caseinolytic proteases (Clps) family (viz. ClpA, ClpB, ClpX, ClpP), Lon and HslVU are reported in S. Typhimurium. In the current study, comparative roles of two such Clps, clpA (involved in proteolysis) and clpB (involved in protein disaggregation and refolding) in the survival of S. Typhimurium under different stresses and in virulence have been investigated. We deleted clpA and clpB genes ( clpA and clpB) from S. Typhimurium and then complemented in trans by pQE60 plasmid. clpB strain was comparatively much more susceptible to 42 °C, HOCl, paraquat and macrophage than clpA strain. As compared to WT and clpA strains, clpB strain was defective for colonization in the poultry caecum and showed decreased dissemination to spleen and liver. Therefore, ClpB is more important than ClpA for survival of S. Typhimurium under stress and virulence in poultry.