The COMMD (COpper Metabolism gene MURR1 Domain) gene family with ten members participates in various biological processes, such as the regulation of copper and sodium transport, NF-κB activity and cell cycle progression. However, studies on the COMMD gene family in amphioxus (Branchiostoma belcheri) are yet largely unknown. In this study, we have identified and characterized the ten COMMD family members from amphioxus (designated as AmphiCOMMDs). Firstly, we clone the full length of AmphiCOMMDs, and all AmphiCOMMD proteins contain the conserved COMM domain with two NES (Nuclear Export Signal) motifs. Secondly, the genomic structure analysis demonstrates that genes of the COMMD family have undergone intron loss and gain during the process of divergence from amphioxus to vertebrates. Thirdly, phylogenetic analysis indicates that AmphiCOMMDs are more closely related to vertebrates, implying the AmphiCOMMDs may be the ancestor of the vertebrate COMMDs. Fourthly, AmphiCOMMDs are ubiquitously and differentially expressed in five investigated tissues (muscles, gills, intestine, heaptic cecum and notochord). Finally, our results show that expression levels of AmphiCOMMD genes are fluctuating after LPS stimulation to some different extent. Taken together, our studies have elaborated the evolutionary dynamic and the innate immune role of the COMMD family genes in amphioxus.