Technical Abstract: Juvenile channel catfish (Ictalurus punctatus) were fed nutritionally complete, practical basal diets supplemented with bovine lactoferrin (Lf) at 0, 200, 400, 800, or 1600 mg/kg diet to apparent satiation twice daily for 5 weeks. Feed intake was significantly higher in fish fed diets supplemented with Lf compared to the control diet, but the increased feed intake did not translate to significant increases in growth performance (weight gain, feed efficiency ratio, or survival). Hemoglobin, white and red blood cell counts, and resistance to low-water stress were also not different among dietary groups (P > 0.05). However, levels of Lf in diets had a significant effect on survival of channel catfish following challenge with Edwardsiella ictaluri. Catfish fed 800 or 1600 mg/kg Lf had higher survival to E. ictaluri infection than the groups fed the control and 200 mg Lf diet. There was not a corresponding increase in activity of immune parameters (plasma lysozyme, hemolytic complement, and bactericidal activities or agglutination antibody titer) with addition of Lf to diets, but plasma iron decreased significantly in channel catfish fed increasing dietary concentrations of Lf. The ability of Lf to sequester iron, an essential nutrient required for the growth of bacteria, is regarded as one of its key antibacterial properties. The increased resistance to disease seemed to correspond with a decrease in plasma iron concentrations and not enhancement of non-specific or specific immune functions. The results from this work corroborate our previous research with Nile tilapia.