The objective of this small-scale study was to evaluate effects of yeast cell wall (YCW) supplementation in weaned piglet’s diet on gut health and integrity. The trial was conducted with 12 piglets, 28-d old (8.5 ± 1.5 kg), distributed in a complete randomized design, with 2 treatments (0 and 2kg/MT of YCW from Saccharomyces cerevisiae), 6 reps, 1 piglet in each. On d 1 of trial, E. coli was inoculated at 9.8 × 10⁸ cfu/mL per pig. The experimental period was 14 d, where on d 1, 1 animal of control group (CG) was killed for baseline values; on d 7, 3 piglets from each treatment were killed; and on d 14, the remaining piglets were killed. Intestinal samples were collected from jejunum on d 1, 7, and 14 and measured under the light microscope for villus height (VH,μm), villus width (VW,μm), mucosal thickness (MT,μm), crypt depth (CD,μm) and villous surface area (VSA,μm²). Also scanning electron microscopy (SEM) was performed. The jejunal samples were also used to determine E. coli (JEC) and total coliform counts (JCC). On d 4, 7, 11, and 14 of the trial, fecal samples of all pigs were also collected for E. coli (FEC) and total coliform count (FCC). The data were analyzed using the GLM (SAS), and means were compared by t-test (P = 0.05). Overall (d 7 and 14), the YCW-treated piglets differed (P < 0.05) from baseline piglet for VH, VW and CD. The CG had better results (P < 0.05) for VH, VW, CD and VSA at 7th d post-infection. However, at 14 d post-infection, YCW supplementation had improved (P < 0.05) VH, CD and VSA. Although there were no statistical differences (P > 0.05) between treatments for MT at d 14, it was numerically improved (+16.2μm) for piglets supplemented with YCW. For SEM, YCW group appeared to have less erosion in villi apices and better microvilli surface, when compared with CG at d 7 and 14. The JEC, JCC, FEC and FCC average of YCW group and CG showed a significant increase (P < 0.05) among the days post-infection, compared with the baseline values; however, the averages of YCW group were significantly lower (P < 0.05) than the CG. These results demonstrated that YCW supplementation at 2 kg/MT to weaned piglets decreased jejunal and fecal E. coli counts and improved intestinal integrity.