Intravenous ketamine, often administered concomitantly with midazolam, is one of the most commonly used drugs for procedural sedation in children. Although it is considered safe for use in children, ketamine can increase intracranial pressure. Hence, this study was carried out to determine whether adding ketamine to midazolam prior to performing lumbar puncture would be associated with a higher cerebrospinal fluid opening pressure in children with suspected aseptic meningitis. Thirty-nine children aged 6 months to 14 years were included: 26 in group A (intravenous midazolam plus ketamine) and 13 in group B (intravenous midazolam only). Mean cerebrospinal fluid opening pressure in group A was 24.4 cm H2O (median 23 cm H2O) compared with 20 cm H2O (median 19.8 cm H2O) in group B (P = .011). Intravenous ketamine prior to performing lumbar puncture is associated with a significantly higher lumbar cerebrospinal fluid opening pressure in children with aseptic meningitis. However, no outcome differences have been found between the two groups.