Hypotensive-hyporesponsive episodes are rare events after immunizations performed for diphtheria, tetanus, Haemophilus influenzae type b and hepatitis B virus vaccines, but most of the reported episodes have been associated with pertussis-containing vaccines. We report the case of a 3-month-old girl, previously healthy otherwise, presenting with the unusual event of a hypotonic-hyporesponsive episode after vaccination with the 13-valent pneumococcal vaccine. Diagnosis was established after a thorough evaluation of the patient and by exclusion of other clinical conditions.