Streptococcus suis is a zoonotic pathogen causing serious infections in both swine and humans. Although metals are essential for life, excess amounts of metals they are toxic to bacteria. when accumulated in excess amounts. Except for zinc, Transcriptome-level data of the mechanisms for resistance to metal-induced toxicity in S. suis are available for no metals other than zinc. have not been investigated from the transcriptome level in S. suis. Herein, we explored the transcriptome-level changes of in S. suis in response to ferrous iron and cobalt toxicity by RNA sequencing. Many A lot of genes were differentially expressed in the presence of excess ferrous iron and cobalt. Most of the genes in response to cobalt toxicity showed the same expression trends as those were expressed in the same trend in response to ferrous iron toxicity. qRT-PCR analysis of the selected genes confirmed the accuracy of RNA sequencing results. Bioinformatics analysis of the differentially expressed genes indicated that ferrous iron and cobalt have similar impacts effects on the cellular processes of S. suis. Treatment with ferrous Ferrous iron treatment resulted in down-regulation of several oxidative stress tolerance-related genes involved in oxidative stress tolerance and up-regulation of the genes in an amino acid ABC transporter operon. Expression of the several genes in the arginine deiminase system was down-regulated in the presence of after ferrous iron and cobalt treatment. Collectively, our results suggested that S. suis alters the expression of a lot of multiple genes to respond to ferrous iron and cobalt toxicity.