We report a rare case of congenital syphilis (CS) presenting as Jarisch–Herxheimer reaction (JHR) at birth. The mother (primigravida) presented in labor and had not received antenatal care. She was given prophylactic ampicillin 2 g i.v. on admission and delivered shortly thereafter. The male infant (2899 g) had normal vital signs, conjunctival congestion, splenohepatomegaly, and maculopapular rash with small blisters over the entire body. Serological tests on the infant and mother confirmed CS. The infant was given i.v. ampicillin for 14 days (50 mg/kg per day until day 3, 100 mg/kg per day thereafter). One hour after the first injection, the infant developed fever (39°C), tachycardia and tachypnea without worsening of rash. Vital signs improved gradually. The rash reduced markedly at postnatal day 1, and disappeared without pigmentation at day 3. This was considered a JHR following ampicillin injection given to the mother before delivery and to the infant after birth.