OBJECTIVE: This study aimed to investigate the impact of different level of soybean meal (SBM) replaced by soy protein concentrate on intestinal health and growth performance of nursery pigs under F18+ Escherichia coli (E. coli). METHODS: Forty-eight newly weaned pigs (6.6±0.3 kg) were randomly allotted to 4 treatments arranged by 2×2 factors using randomized complete block design with initial body weight and sex as blocks. Two factors were F18+ E. coli challenge (0 or 2.1×1010 colony-forming units [CFU]) and the level of SBM (24% or 12% in phase 1 and 26% or 14% in phase 2). Pigs were fed for 25 d in 2 phases (phase 1 for 11 d and phase 2 for 14 d). At the end of study, all pigs were euthanized to collect jejunal mucosa and tissues. RESULTS: The F18+ E. coli challenge decreased (p<
0.05) overall average daily gain (ADG) and average daily feed intake (ADFI) and decreased (p<
0.05) gain to feed ratio on d 7 to 11. The high SBM tended to have a greater overall ADG (p = 0.054) and ADFI (p = 0.078) compared with low SBM under F18+ E. coli challenge, but not in unchallenged conditions. The F18+ E. coli challenge increased (p<
0.05) fecal score on d 7 to 18. The tumor necrosis factor-α and interleukin-1β in jejunal mucosa were decreased (p<
0.05) in high SBM treatments. The high SBM tended to increase (p = 0.085) occludin expression in jejunum. high SBM increased crypt depth in jejunum under F18+ E. coli challenge, but not in unchallenged conditions (p<
0.05). CONCLUSION: High SBM in nursery diets could alleviate the detrimental effects of F18+ E. coli challenge on growth performance of pigs under compared to low SBM inclusion, which might be attributed to decreased intestinal inflammation and improved intestinal integrity.