The sulfate reducing bacterium Desulfovibrio desulfuricans inhabits both the human gut and external environments. It can reduce nitrate and nitrite as alternative electron acceptors to sulfate to support growth. Like other sulphate reducing bacteria, it can also protect itself against nitrosative stress caused by NO generated when nitrite accumulates. By combining in vitro experiments with bioinformatic and RNA-seq data, metabolic responses to nitrate or NO and how nitrate and nitrite reduction are coordinated with the response to nitrosative stress were revealed. Although nitrate and nitrite reduction are tightly regulated in response to substrate availability, the global responses to nitrate or NO were largely regulated independently. Multiple NADH dehydrogenases, transcription factors of unknown function and genes for iron uptake were differentially expressed in response to electron acceptor availability or nitrosative stress. Amongst many fascinating problems for future research, the data revealed a YtfE orthologue, Ddes_1165, that is implicated in the repair of nitrosative damage. The combined data suggest that three transcription factors coordinate this regulation in which NrfS-NrfR coordinates nitrate and nitrite reduction to minimize toxicity due to nitrite accumulation, HcpR1 serves a global role in regulating the response to nitrate, and HcpR2 regulates the response to nitrosative stress.