Epiploic appendagitis (EA) is an uncommon intraabdominal pathology resulting in transient, localized pain. The condition is caused by ischemia of one of the epiploic appendages, which are distributed axially along the length of the colon. EA is often mistaken for other more common etiologies of an acute abdomen. Generally, the patients experience focal abdominal pain with no further symptoms or laboratory abnormalities. The authors encountered a 79-year-old male with severe sepsis and acute respiratory failure requiring intubation. He recovered rapidly after the identification and removal of a single EA. This paper reports the first case of EA leading to the systemic dysregulation of sepsis.