The circadian system regulates many important aspects of physiology, including the immune response to infectious agents, which is mediated by the activation of the transcription factor NF-kappa B. Thus, understanding the mechanisms by which circadian clocks regulate NF-kappa B is a necessary step toward the development of improved therapies underwritten by NF-kappa B manipulation. Previous reports have identified OTUD7B a deubiquitinase, as a novel regulator of noncanonical NF-kappa B signaling, largely through the maintenance of TRAF3, a negative regulator of NF-kappa B. In investigations in our laboratory, when the Clock gene was repressed by shRNA, the results of microarray analysis demonstrated that Otud7b was down-regulated. Further research by real-time PCR and western blot revealed that that Otud7b exhibits rhythmic mRNA expression. These findings confirm Otud7b as a novel clock-regulated gene. Additionally, Otud7b may be an important bridge between the circadian system and noncanonical NF-kappa B pathway regulation.