The RpoS/σ^S sigma subunit of RNA polymerase is the master regulator of the general stress response in many Gram-negative bacteria. Extensive studies have been conducted on σ^S-regulated gene expression at the transcriptional level. In contrast, very limited information regarding the impact of σ^S on global protein production is available. In this study, we used a mass spectrometry-based proteomics approach to explore the wide σ^S-dependent proteome of the human pathogen Salmonella enterica serovar Typhimurium. Our present goals were twofold: (1) to survey the protein changes associated with the ΔrpoS mutation and (2) to assess the coding capacity of σ^S-dependent small RNAs. Our proteomics data, and complementary assays, unravelled the large impact of σ^S on the Salmonella proteome, and validated expression and σ^S regulation of twenty uncharacterized small proteins of 27 to 96 amino acids. Furthermore, a large number of genes regulated at the protein level only were identified, suggesting that post-transcriptional regulation is an important component of the σ^S response. Novel aspects of σ^S in the control of important catabolic pathways such as myo-inositol, L-fucose, propanediol, and ethanolamine were illuminated by this work, providing new insights into the physiological remodelling involved in bacterial adaptation to a non-actively growing state.