Cecal ligation and puncture (CLP) is referred to as the "gold standard" rodent model for abdominal sepsis. CLP creates a continuously leaking, polymicrobial infectious focus in the abdomen. The abdominal cavity is opened under general anesthesia and analgesia and the cecum is exposed, ligated underneath the ileocecal valve, and punctured with a needle. A small amount of feces is pressed out through the puncture and the cecum is repositioned into the abdomen, which is then closed with single button sutures and tissue glue. CLP severity can be influenced via the length of the ligated cecum as well as the needle size. Within 24 h, animals develop clinical signs of a systemic bacterial infection. Analgesia, wide range antibiotic treatment, and fluid resuscitation should be administered during the acute phase of sepsis to increase the clinical relevance of the CLP model.