Central nervous system (CNS) infection is a rare complication of endoscopic injection sclerotherapy (EIS) for esophageal varices. We report two patients, one of whom developed a solitary brain abscess, and the other, acute meningitis, after EIS. They presented with high fever initially, and then with changes in mental status. In the case of the solitary brain abscess, the CSF revealed evidence of infection, and CT scan disclosed a brain abscess in the left temporo-parieto-occipital region. This patient received EIS six times and developed the CNS complication 4 wk after the last EIS. There was no growth in either the CSF or the abscess cultures in this case. The other patient with acute meningitis, which developed on the second day after the second session of EIS, had a positive CSF culture of Klebsiella pneumoniae. Both of these patients died despite antibiotic treatment, and craniotomy with drainage in the patient with a brain abscess.