Thirty-six piglets weaned on day 21 were used to investigate the effect of dietary crude protein (CP) and non-pathogenic Escherichia coli probiotic on performance of piglets subjected to E. coli K88 challenge in a 12-d study. A 2×3 factorial arrangement with two levels of CP (HP, 22% vs LP 17%) and three additives types (no additive, NA; in-feed antibiotic, AB; and probiotic, PRO) constituted the 6 treatments. The PRO diets were prepared each morning by mixing 50ml of 9×10 10 cfu/ml of fresh probiotic cultures with fresh feed. After a 6-d adaptation period, pigs were orally inoculated with a 6ml of E. coli K88 (2×10 10 cfu/ml). Pigs fed the LP diets had higher ADG during pre- and post-inoculation period than pigs fed the HP diets. The LP fed pigs plus PRO had superior (P<0.05) ADG post-inoculation compared to the AB treatment. Pigs fed with LP diets had lower (P<0.05) post-inoculation FC scores than pigs fed with HP diets. Ileal mucosal counts of E. coli K88 were lower (P<0.05) for the AB and PRO treatments 7d post-challenge than other treatments. In conclusion, the 17% dietary CP level resulted in superior performance in piglets than 22% dietary CP level and the LP diet and E. coli-based probiotic acted synergistically resulting in better performance in post-weaning piglets.