Pneumococcal Ser/Thr kinase (StkP) and its cognate phosphatase (PhpP) play a crucial role in bacterial cytokinesis. However, their individual and/or reciprocal metabolic and virulence regulation-related roles as in the case of other Gram-positive pathogens, have not been adequately investigated especially in encapsulated pneumococci. Here, we demonstrate that the mutants lacking PhpP and StkP derived from the encapsulated pneumococcal strain D39 displayed differential cell division defects, and growth patterns, when grown in semisynthetic media supplemented with glucose or non-glucose sugars as the sole carbon source. Microscopic and biochemical analyses supported by RNA-seq-based global transcriptomic analysis of these mutants revealed significant down- and up-regulation of the capsule formation and genes (cps2) in D39ΔPhpP and D39ΔStkP mutants respectively. While StkP and PhpP individually regulated several unique genes, both of them participated in sharing regulation of the same set of differentially regulated genes. The reciprocal regulation of cps2A genes was found to be in part by the StkP/PhpP-mediated reversible phosphorylation-modulated binding of CcpA to the cps2A promoter (Pcps2A) and was independent of MapZ-regulated cell division process. In particular, the increasing StkP-mediated phosphorylation of CcpA proportionately inhibited the binding of CcpA to the Pcps2A. While the attenuation of virulence of the D39ΔPhpP mutant in two mouse infection models corroborated with several down-regulated capsules-, virulence- as well as PTS-related genes, the D39ΔStkP mutant, despite possessing increased capsule displayed significantly decreased virulence in mice. The ability of StkP and PhpP to regulate multiple key pneumococcal cellular activities suggests that they may serve as important targets for the development of novel therapeutics.