Acute appendicitis is a rare condition in the neonatal period and has been reported to be associated with other diseases such as premature infants, cystic fibrosis, and necrotizing enterocolitis (NEC). We describe a case of acute appendicitis in a 26-day-old newborn male presented with abdominal distension, grunting, and vomiting. He was 38.8 weeks gestation, obtained by cesarean section. He had no additional risk factor except he had a history of hyperosmolar formula feeding for several days, fed by his mother for weight gain. Despite fasting and broad-spectrum antibiotic treatment, the clinical course did not improve and deteriorate. The ultrasonography of abdomen showed edematous wall thickening with fluid-filled distension in the distal ileum and otherwise unremarkable. The exploratory laparotomy revealed appendicitis complicated with peritoneal inflammation. Appendectomy and full-thickness rectal biopsy were carried out. The histopathological finding showed acute gangrenous inflammation. Ganglion cells were present on rectal biopsy. Because he had no additional risk factor and hyperosmolar formula feeding is also a risk factor for NEC, it might trigger appendiceal inflammation. Acute appendicitis in the neonate is rare, but the risk of perforation and mortality is high unless it is treated properly. Therefore, it should be considered as a possible cause of abdominal distension and sepsis in the neonatal period. Also, parents should be trained to prepare the formula in a specified manner.