Pyogenic liver abscess (PLA) is a significant cause of mortality if left untreated, with an incidence of 1.07 to 3.59 per 100,000 people in Western countries. PLA can result from various etiologies, including choledocholithiasis, adjacent organ inflammations such as cholecystitis, diverticulitis, and appendicitis. Additionally, immunosuppression plays a key role in the development of PLA. Anti-TNF therapies are commonly used to treat both Ulcerative Colitis (UC) and Crohn’s Disease (CD). Despite the widespread use of anti-TNF therapy in inflammatory bowel disease, pyogenic liver abscesses are rare in these patients. In this report, we present a case of PLA in a patient diagnosed with UC who was undergoing anti-TNF therapy.