Abstract Three studies were conducted to evaluate the potential benefit of a stimbiotic on porcine ear necrosis and the fecal microbiome in nursery pigs. In experiment 1, 600 mixed-sex piglets were randomly placed in 20 pens with 30 pigs/pen (n = 10). The pigs were fed a common wheat and barley-based nursery diet (CON) or CON with stimbiotic (Signis, 0.15g/kg; STB). Incidence of ear necrosis was recorded on individual animals at 28 d post-weaning. Mortality was analyzed using ANOVA and PEN was evaluated using a chi-square test. In experiment 2, a total of 65,200 pigs were placed on trial in 8 nursery barns. Treatments were assigned to a quadrant within each barn (n = 8). Newly weaned pigs were fed a common corn-soy nursery diet (CON) or CON with stimbiotic (Signis, 0.1g/kg; STB). Ear necrosis was classified as either: 1) nominal lesions or 2) moderate to severe lesions and was recorded at 1, 3, and 5 wk post weaning. Mortality and injectable treatments were recorded. Mortality data were analyzed using a binomial regression. A Poisson regression was used to analyze the incidence of PEN and injectable treatment rate with the fixed effect of treatment and random effects of sow farm, site, and barn. In experiment 3, a total of 47,200 pigs in 10 nursery barns were randomly assigned to either a standard nursery diet (CON) or CON with stimbiotic (Signis, 0.1 g•kg-1•ton-1; STB). Mortality was recorded throughout the 6-wk trial and PEN score was recorded at d 42. Fecal samples were collected on 7, 21, and 42 d post-weaning for 16S rRNA sequencing and predictive metabolic function analysis. In experiment 1, no differences in mortality were observed (P > 0.10). A total of 156 pigs in the CON fed group developed PEN, whereas only 27 pigs in the STB group developed PEN (52% vs. 9%; P < 0.01). In experiment 2, there was no difference among treatments for mortality. Pigs fed the STB treatment required 15% fewer injectable treatments than pigs fed the control (P < 0.05). No differences of PEN were observed in wk 1 and 3; however, at 5 wk post-weaning, incidence of PEN was 23% less in pigs fed the STB the the control fed pigs (P < 0.05). In experiment 3, the pigs fed STB had decreased incidence of ear necrosis (3.09% vs 4.08%; P < 0.05) and mortality (2.42% vs 2.86%; P < 0.05), overall reducing PEN and mortality by 32% and 18%, respectively. The fecal microbiome of pigs fed CON was associated with the chondroitin sulfate degradation pathway, an important component of cartilage. In conclusion, feeding a stimbiotic appears to be beneficial in nursery pigs to help alleviate challenges with PEN, which is potentially driven by a beneficial shift in the pig’s microbiome.