Zonisamide, an antiepileptic drug, is excreted into breast milk, but information regarding the safety of breast-feeding while using this drug is limited. We present the cases of two nursing mothers, taking 300 and 100 mg/day zonisamide. At 5 days after delivery, the milk concentrations and relative infant doses of the drug were 18.0 and 5.1 μg/mL, and 44 and 36%, respectively. In the first case, the mother fed colostrum and continued partial breast-feeding thus reducing the relative infant dose to 8%. The neonatal serum concentration of zonisamide declined to below the limit of detection at day 34 after birth. In the second case, the mother breast-fed partially until 2 weeks postpartum. No adverse effect was observed in the infants. These findings suggest that mothers taking zonisamide should not breast-feed exclusively, but may not have to avoid partial breast-feeding, with significant caution regarding adverse effects in infants.