The alternative sigma factor σ(B) of Staphylococcus aureus is involved in the coordination of the general stress response, expression of virulence determinants, and modulation of antibiotic resistance levels. It controls a large regulon, either directly by recognizing conserved σ(B) promoter sequences or indirectly via σ(B)-dependent elements. The σ(B)-controlled yabJ-spoVG operon encodes two such putative downstream elements. We report here transcriptome analysis in S. aureus Newman, showing that inactivation of the yabJ-spoVG operon had primarily a repressing effect on a small subregulon encoding mainly virulence factors, including a nuclease (nuc), a protease (splE) and a lipase (lip). As a consequence, extracellular nuclease, protease, and lipase activities were reduced in a ΔyabJ-spoVG mutant. trans-complementation by SpoVG was sufficient to restore their reduced phenotypic expression and lowered transcription due to the yabJ-spoVG deletion. It did not restore, however, the changes triggered by σ(B) inactivation, indicating that both regulons only partially overlap, despite the σ(B) dependency of the yabJ-spoVG expression. Thus, σ(B) is likely to control additional, SpoVG-independent factors affecting the expression of numerous hydrolytic enzymes. SpoVG, on the other hand, seems to fine-tune the σ(B)-dependent regulation of a subset of virulence factors by antagonizing the σ(B) effect.