Subdural empyema (SDE) is a focal accumulation of pus between the arachnoid and dura matter. In infants and young children, it is usually attributed to meningitis complications. SDE is considered a serious neurological condition and the culprit is usually a single organism. In rare occasions, polymicrobial is the cause and the organisms involved are, usually streptococci and anaerobe bacteria. A search of the PubMed database was carried out, using a combination of the following terms: subdural empyema , infant, and meningitis. The majority studies conducted on infants mentioned one single organism as the cause of subdural empyema. We are presenting a rare, if not unique, case of subdural empyema in an immunocompetent infant due to an unusual combination of Escherichia coli and Neisseria meningitides. Meningitis is a dynamic disease, and its detrimental consequences could be avoided if diagnosed early. It will be crucial to re-sample the CSF looking for additional organism if a patient with meningitis continues to be febrile, despite antibiotics therapy. Although CSF culture is considered the gold standard in identifying the organism in meningitis, it could be missed due to different reasons including technical flaws. Latex bacterial antigen test could be an indispensable ancillary technique in the diagnosis of meningitis and hence treatment.