We report a case of early onset sepsis caused by (CTX for cefotaximase and M for Munich)-type extended-spectrum β-lactamase-producing Escherichia coli (ESBL E. coli) in a preterm infant weighing 601 g. He was given meropenem and treated for endotoxin absorption with polymyxin B-immobilized fibers with only 8 mL of priming volume. The patient survived without any short-term neurological or respiratory sequelae. The choice of antibiotics is particularly important in seriously ill neonates with sepsis due to ESBL-producing organisms. Polymyxin B hemoperfusion might be an innovative therapy for severe neonatal sepsis and could improve outcome even in an extremely low-birthweight infant.