Clostridium difficile colitis has been the most recognized bacterial enterocolitis for years and other bacteria such as Staphylococcus colitis has been relegated. Staphylococcus enterocolitis following antibiotics had been one of the most frequent complications in surgical patients in the 1950s and 1960s and now reappear with more resistance such as methicillin-resistant(MRSA) colitis which brings a new challenge. A 32-year-old Hispanic female with a history of type I diabetes mellitus presenting with altered sensorium and a 2-day history of watery, nonbloody diarrhea, intractable emesis, and diffuse crampy abdominal pain. About a month before the presentation, the patient had a soft-tissue laceration on the left foot requiring a 7-day course of cephalexin and clindamycin that healed appropriately. On physical examination, she was tachycardic with heart rate of 110 bpm and tachypneic with respiratory rate of 28, somnolent but arousable with the Glasgow Coma Scale >12. The abdomen was soft, tender diffusely to palpation without rebound or guarding. On the biochemical analysis, her blood glucose was 968 mg/dL with anion gap metabolic acidosis (AG 46). In the intensive care unit, she initiated on intravenous (IV) fluids, insulin, and IV antibiotics for suspicion of colitis. Clostridium difficile testing was negative, but stool cultures grew MRSA for which she was started on vancomycin and TMP-SMX. Due to continued abdominal pain on antibiotics, computed tomography of the abdomen with contrast showed acute appendicitis with inflammatory debris and without perforation or abscess requiring laparoscopic appendectomy. Our case presented with diabetic ketoacidosis (DKA), which complicates the etiology of abdominal pain on admission for the clinician masking-MRSA colitis associated with a rare complication of appendicitis double challenge and difficult to diagnose as most DKA patients present with abdominal pain. This is the first case report describing MRSA enterocolitis in patient with DKA complicated by acute appendicitis.