Technical Abstract: Infection and inflammation are often accompanied by oxidative stress caused by the accumulation of reactive oxygen species which can be deleterious to the health of the host. Antioxidant defense mechanisms and components are crucial in limiting cellular and tissue-level damage and restoring homeostasis. In mammals, calreticulin is a 46-kDa multifunctional calcium binding protein of the endoplasmic reticulum that has many critical functions in the eukaryotic cell including regulation of intracellular calcium homoeostasis, lectin binding and chaperoning, and oxidative stress responses. In previous studies from our lab, the calreticulin gene was observed to be strongly upregulated in catfish during challenge with infectious Gram-negative bacteria. However, little is known about the function of this gene in teleost fish. The objective of this study, therefore, was to characterize the calreticulin gene from channel catfish, to determine its genomic organization, to profile its patterns of tissue expression, and to establish its potential for physiological antioxidant and immune responses in catfish after bacterial infection with Edwardsiella ictaluri and iron treatment. Our results indicate that there are at least three calreticulin related genes in the catfish genome. The three calreticulin genes are widely expressed in various tissues under homeostatic conditions and their expression showed significant upregulation following infection and/or iron level changes.