Lice infestation is a commonly encountered disorder in emergency medicine. The louse survives from a blood meal from its host; hence, iron deficiency anemia is a theoretic possibility. A limited number of reports of severe iron deficiency anemia have appeared in the veterinary literature, but a thorough review of the medical literature did not reveal a single instance in human beings.We report a small case series of patients with heavy louse infestation and profound iron deficiency anemia.The index case along with two other cases discovered from an exhaustive search of 4 years of the institution's Emergency Department records all had heavy infestation with head and body lice. Laboratory evaluation revealed serum hemoglobin levels under 6 gm/dL, low serum ferritin levels, and microcytic red blood cell indices. All patients were admitted to the hospital, received transfusions, and had evaluation of their anemia. No patient had evidence of gastrointestinal blood loss or alternative explanation for their anemia.Although cause and effect cannot be established from this case series, to the best of our knowledge, this is the first published evidence of a provocative association of louse infestation and severe iron deficiency anemia in humans.