Abstract Dietary fiber has been shown to promote a healthy gut microbiota, while stimbiotics enhance fermentable substances and boost the expansion of the commensal microbiome, improving host health by alleviating deleterious effects of proinflammatory responses. The intended purpose of this study was to gain an understanding of the effectiveness of dietary fiber sources and stimbiotic on the sustainability of F18 enterotoxigenic Escherichia coli (ETEC) challenge. A total of 216 piglets were blocked (n = 8) by weaning body weight (BW) and randomly assigned to 1 of 4 dietary treatments, including corn-SBM based control diet (CC), high fiber diet (HF: 5.0, 3.8. 2.5% sugar beet pulp and 4.0, 3.0 and 2.0% soy hulls for phases 1, 2, and 3, respectively), CC plus 0.01% stimbiotic (CS: Signis, ABVISTA Marlborough, UK), and HF plus 0.01% stimbiotic (FS). Pigs were fed a four-phase feeding regimen: phase 1 (d 0-9), phase 2 (d 9-16), phase 3 (d 16-22), phase 4 (d 22-41). Dietary fiber and stimbiotic were provided from weaning (d 0) to d 22, and then a common diet was fed from d 22 to the end of the trial. On d 5 postweaning, all pigs were orally inoculated with 10 mL of F18 ETEC (108 CFU/mL). One median BW pig from each pen was selected at weaning for fecal sampling. Before the challenge, the same pigs were sampled on d 5 and again on d 8 and d12. Samples were used to quantify the E. Coli using 3M Petrifilm (3M Food Safety, St. Paul, MN) and virulence genes of the isolate were qualified using multiplex PCR. Colony-forming-count was log-transformed. All data normality was verified using Univariate procedure and analyzed using Mixed procedure of SAS (Cary, NC). Pigs fed both CS and HF increased average daily gain (ADG) in phase 2 and phase 1-3 compared with pigs fed CC diets, while adding stimbiotic had no additional benefit to HF (Fiber×Stimbotic P = 0.03 and 0.06, respectively). This response led to heavier BW in pigs fed CS at the end of phase 3 compared with pigs fed CC with HF and FS as intermediate (Fiber×Stimbotic P = 0.06, respectively). Overall, average daily feed intake (ADFI) was greater in pigs fed CS than pigs fed FS while no difference was found between CC and CF (Fiber×Stimbotic P = 0.02). Dietary fiber did not impact gain to feed ratio (G:F); however, G:F was improved in stimbiotic fed pigs in phase 2 (Stimbiotic P = 0.01). Total coliform count was reduced from d 2 to d 7 (day; P < 0.01), but neither fiber nor stimbiotic altered the coliform count. Results of this study demonstrated that both high fiber and stimbiotic help restore ADG when pigs were challenged with ETEC. Additionally, stimbiotic also benefited feed efficiency and resulted in the heaviest BW.