BACKGROUND: Soft-coated wheaten terriers (SCWTs) have a predisposition to the development of protein-losing enteropathy (PLE). Early recognition of disease may improve morbidity and mortality in these and other at-risk dogs. Preclinical inflammatory bowel disease (IBD), characterized by increased intestinal permeability, immune dysregulation and inflammation, and changes to the gut microbial composition, or biochemical evidence of disease many years before development of clinical signs, has been proposed for people at risk for IBD. HYPOTHESIS/OBJECTIVES: Determine if changes in fecal metabolites and intestinal permeability could be identified in SCWTs before development of clinical signs. We hypothesized that, in contrast to healthy non-SCWT dogs, healthy SCWT would have changes similar to those of dogs with PLE. ANIMALS: Twelve healthy SCWTs, 10 healthy non-SCWTs, and 8 PLE dogs. METHODS: Prospective study. Fecal calprotectin, targeted metabolites and unconjugated bile acids, intestinal permeability testing, and video capsule endoscopy were evaluated. Single-factor analysis of variance (ANOVA) was performed to evaluate fecal metabolites and bile acids for group differences. A repeated-measures mixed model ANOVA was performed for blood lactulose:galactose area under the curve (AUC). RESULTS: Significant differences among groups were found for several fecal fatty acids and sterols. Healthy non-SCWT dogs, but not healthy SCWTs, were found to have significantly lower AUCs than PLE dogs (P = .04). CONCLUSIONS: Healthy SCWT dogs had changes in several biomarkers used to identify preclinical IBD in humans.