The main role of CodY, a global regulatory protein in most low G + C gram-positive bacteria, is in transcriptional repression. To study the functions of CodY in Streptococcus suis serotype 2 (S. suis 2), a mutant codY clone named ∆codY was constructed to explore the phenotypic variation between ∆codY and the wild-type strain. The result showed that the codY mutation significantly inhibited cell growth, adherence and invasion ability of S. suis 2 to HEp-2 cells. The codY mutation led to decreased binding of the pathogen to the host cells, easier clearance by RAW264.7 macrophages and decreased growth ability in fresh blood of Cavia porcellus. The codY mutation also attenuated the virulence of S. suis 2 in BALB/c mice. Morphological analysis revealed that the codY mutation decreased the thickness of the capsule of S. suis 2 and changed the surface structures analylized by SDS-PAGE. Finally, the codY mutation altered the expressions of many virulence related genes, including sialic acid synthesis genes, leading to a decreased sialic acid content in capsule. Overall, mutation of codY modulated bacterial virulence by affecting the growth and colonization of S. suis 2, and at least via regulating sialic acid synthesis and capsule thickness.