Abstract: Up to thirty piglets with an average live body weight of 5.9±0.5 kg were challenged using enterotoxigenic Escherichia coli and randomly assigned to three treatment groups fed a corn-soybean meal-based diet containing either no addition (control group), 0.1 g kg-1 of lactoferrampin-lactoferricin (lactoferrampin-lactoferricin group) or 0.1 g kg-1 of chlortetracycline (chlortetracycline group) for 21 days. Compared with the control group, dietary supplementation with lactoferrampin-lactoferricin or chlortetracycline increased the body weight and daily weight gain and decreased the feed to gain ratio, diarrhea rate and serum IgM and IgG levels (p<0.05). The serum levels of IL-1β, IL-6, TNF-α, diamine oxidase and endothelin-1 were not significantly different among all treatment groups (p>0.05). Compared with the control group, dietary supplementation with lactoferrampin-lactoferricin changed the serum concentrations of 10 amino acids (p<0.05); dietary supplementation with chlortetracycline only changed the serum histidine concentration (p<0.05). These results indicate that lactoferrampin-lactoferricin and chlortetracycline have similar effects on piglets weaned at 21 days of age which is expected to have practical applications in the livestock industry.