Streptococcus equi subsp. zooepidemicus (S. equi subsp. zooepidemicus), which carries the Lancefield group C antigen, is an uncommon human pathogen. It is considered an opportunistic commensal of the equine upper respiratory tract and causes invasive infections in immunocompromised hosts, following close contact to infected horses. Meningitis caused by S. equi subsp. zooepidemicus is a rare infectious disease with high rates of complications. We present the case of a 56-year-old female with acutely altered mental status following three days of fever and vomiting. For several months, she was taking care of horses. The most relevant preexisting illnesses were chronic hepatitis C infection and traumatic paraplegia due to spinal cord injury 30 years ago. Laboratory evaluation on admission revealed leukocytosis, hyponatremia, and elevated C-reactive protein. Cerebral CT scan showed diffuse cerebral edema. Whereas cerebrospinal fluid real-time PCR assay for common pathogens was negative, cultures showed S. equi subsp. zooepidemicus. She recovered fully after intravenous administration of ceftriaxone for four weeks. This is one of only few reported cases of S. equi subsp. zooepidemicus meningitis and the first case in chronic hepatitis C infection. Our case supports the necessity for extended microbiological examination especially in immunocompromised patients if PCR examination for common pathogens is negative.