Background: Acute meningoencephalitis is an important cause of morbidity and mortality around the globe. The objective of this study was to examine the distribution of acute meningoencephalitis and its aetiological agents among children admitted to a tertiary hospital in southern Bangladesh. Methods: This prospective study was carried out in Khulna Medical College Hospital from 2007 to 2009. All of the admitted children between 1 month and 12 years of age were enrolled over a 2-year period if they met the inclusion criteria of having an acute onset of fever (≤ 14 days) and any of the following 3 signs: neck stiffness, convulsion, or altered mental status. Cerebrospinal fluid (CSF) was collected within hours and sent to the laboratory for cytological and biochemical analyses. CSF was examined by Gram staining and a latex agglutination test to detect common bacteria. Serum and CSF were also tested for Japanese encephalitis virus antibodies. Results: A total of 140 children were included in the study, which accounted for 2.5% of admissions between 2007 and 2009. The number of acute meningoencephalitis cases was relatively higher (37.9%) during the monsoon season. The CSF report revealed a pyogenic form in 24 (18.5%) and a viral form in 13 (10.0%) cases. Altered mental status was significantly less frequent (P < 0.001) in cases of pyogenic meningoencephalitis (62.5%) than in cases of non-pyogenic meningoencephalitis (93.4%). Bacterial causes were identified in 11 (8.5%) children; the causative agents included Streptococcus pneumoniae (n = 8), Neisseria meningitides (n = 2), and Haemophilus influenzae (n = 1). Three (2.3%) patients were positive for Japanese encephalitis virus. Conclusion: S. pneumoniae was the most common bacteria causing acute meningoencephalitis among the study subjects, and Japanese encephalitis virus was present in few patients.