T cell exhaustion is the main cause of sepsis-induced immunosuppression, and is associated with the poor prognosis. Nicotinamide adenine dinucleotide (NAD+) is well known for its anti-aging effect, but its role in sepsis-induced T cell exhaustion remains to be elucidated. In the present study, using a classic septic animal model, we found that the levels of NAD+ and its downstream molecule-sirtuins 1 (SIRT1) in T cells in sepsis were decreased. Supplementation with Nicotinamide ribose (NR), the precursor of NAD+, right after cecal ligation and puncture significantly increased the levels of NAD+ and SIRT1...Additionally, the bacteria load, organ damage (lung, heart, liver and kidney) and the mortality of septic mice were reduced after NR supplementation. In summary, these results demonstrate the beneficial effect of NR on sepsis and T cell exhaustion, which is associated with NAD+/SIRT1 pathway.