Lactoferrin has antimicrobial activity associated with peptide fragments lactoferricin (LFC) and lactoferrampin (LFA) released on digestion. These two fragments have been expressed in Photorhabdus luminescens as a fusion peptide linked to protein cipB. The construct cipB–LFC–LFA was tested as an alternative to antimicrobial growth promoters in pig production. Sixty piglets with an average live body weight of 5·42 (sem 0·59) kg were challenged with enterotoxigenic Escherichia coli and randomly assigned to four treatment groups fed a maize–soyabean meal diet containing either no addition (C), cipB at 100 mg/kg (C+B), cipB–LFC–LFA at 100 mg/kg (C+L) or colistin sulfate at 100 mg/kg (C+CS) for 3 weeks. Compared with C, dietary supplementation with C+L for 3 weeks increased daily weight gain by 21 %, increased recovery from diarrhoea, enhanced serum glutathione peroxidase (GPx), peroxidase (POD) and total antioxidant content (T-AOC), liver GPx, POD, superoxide dismutase and T-AOC, Fe, total Fe-binding capacity, IgA, IgG and IgM levels (P < 0·05), decreased the concentration of E. coli in the ileum, caecum and colon (P < 0·05), increased the concentration of lactobacilli and bifidobacteria in the ileum, caecum and colon (P < 0·05), and promoted development of the villus–crypt architecture of the small intestine. Growth performance was similar between C+L- and C+CS-supplemented pigs. The present results indicate that LFC–LFA is an effective alternative to the feed antibiotic CS for enhancing growth performance in piglets weaned at age 21 d.