RopB is a quorum-sensing regulator that binds to the SpeB-inducing peptide (SIP) under acidic conditions. SIP is known to be degraded by the endopeptidase PepO, whose transcription is repressed by the CovR/CovS two-component regulatory system. Both SIP-bound RopB (RopB-SIP) and SIP-free RopB (apo-RopB) can bind to thespeBpromoter; however, only RopB-SIP activatesspeBtranscription. In this study, we found that the SpeB expression was higher in theropBmutant than in the SIP-inactivated (SIP*) mutant. Furthermore, the deletion ofropBin theSIP* mutant derepressedspeBexpression, suggesting that apo-RopB is a transcriptional repressor ofspeB. Up-regulation of PepO in thecovSmutant degraded SIP, resulting in the down-regulation ofspeB. We demonstrate that deletingropBin thecovSmutant derepressed thespeBexpression, suggesting that thespeBrepression in this mutant was mediated not only by PepO-dependent SIP degradation but also by apo-RopB. These findings reveal a crosstalk between the CovR/CovS and RopB-SIP systems and redefine the role of RopB in regulatingspeBexpression in group AStreptococcus.