Background/Objectives: Systemic levels of the adipokine adiponectin are elevated in chronic liver disease including primary sclerosing cholangitis (PSC). Inflammatory bowel disease (IBD) and PSC are closely associated diseases, but in IBD serum adiponectin levels are near normal. Urinary and fecal biomarkers have been suggested to be superior to the corresponding serum protein for disease diagnosis, but urinary and fecal adiponectin have not been analyzed in PSC. The aim of this study was to evaluate the adiponectin in human serum, urine, and feces as a potential diagnostic tool for PSC. Methods: Serum and urine samples were collected from 74 IBD patients, 40 PSC patients (35 patients with PSC and IBD (16 patients for urine) and 5 patients with PSC without underlying IBD), and 17 controls. Feces samples from 53 IBD patients and 11 PSC patients (8 of them with PSC-IBD) were available for this study. Adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Results: Urinary and serum adiponectin levels in IBD patients and controls were comparable. Urinary, fecal and serum adiponectin in patients with ulcerative colitis and Crohn’s disease were similar and did not change, even with higher fecal calprotectin, a marker of intestinal inflammation in IBD. The three IBD patients with a high Gastrointestinal Symptom Rating Scale score as a marker for clinical activity had highly elevated urinary adiponectin. Systemic adiponectin levels were significantly elevated in the PSC-IBD cohort relative to the IBD-only group, suggesting its potential utility in clinical screening. Urinary and fecal adiponectin levels were similar between the cohorts. In PSC/PSC-IBD, serum adiponectin did not increase with higher fibrosis scores. Serum, urine, and fecal adiponectin were not correlated in both patient cohorts, except for a negative association of fecal and urine adiponectin in PSC. Conclusions: This exploratory study revealed preliminary findings suggesting an association between urinary adiponectin and severe gastrointestinal symptoms in IBD. In PSC-IBD, serum adiponectin is higher compared to IBD patients and continuous measurement may be used for PSC-IBD screening.