Atypical hemolytic uremic syndrome (aHUS) is a rare form of complement dysregulation disease, and recently various reports have shown that it is associated with one or more mutations in the complement regulatory genes including complement factor H (CFH). Plasma exchange is a therapeutic option for adult patients, but not for a very young infant because of a potential side effect of therapeutic plasma exchange (TPE) itself. Herein, we describe a case of successful treatment of early onset aHUS associated with a novel CFH mutation with total 21 sessions of TPE over a period of 46 days in 3.2 kg 23-day-old neonate. J. Clin. Apheresis, 2011. © 2011 Wiley-Liss, Inc.