Design This retrospective study was carried out at the Department of Pathology, University College Hospital, Ibadan, Nigeria. Aim The aim of the study was to determine the pattern of CNS infections seen in the Department of Pathology, UCH, Ibadan. Methods Autopsy records of CNS infections diagnosed at the Department of Pathology, University College Hospital, Ibadan between January 1981 and December 2006 were reviewed. Information on age, sex, clinical presentation, anatomical location and gross and microscopic findings were retrieved and the glass slides were reviewed, where available. Results There were 408 CNS infections, with a progressive decline in the frequency of CNS infection diagnosed at autopsy during the study period. The male to female ratio was 1.3:1 and the patients ranged from 2 to 81 years of age, with 186 (45.6%) cases occurring in children aged 9 years and below. The most common CNS infections were pyogenic meningitis (54.9%), tuberculous meningitis (21.6%) and cerebral malaria (12.7%). A correct ante-mortem diagnosis of pyogenic meningitis, tuberculous meningitis, cerebral malaria and brain abscess was made in 41.5%, 19.3%, 40.4% and 11.5% of the cases, respectively. Conclusion CNS infections are often diagnosed late or are misdiagnosed, resulting in considerable morbidity and mortality. There is a need for a high clinical index of suspicion on the part of clinicians.