More than 1,000 children under 5 years of age die every day from malaria. Cerebral malaria (CM) is the most severe and deadly manifestation of the disease. The occurrence of multiple organ dysfunction syndrome (MODS) has been associated with increased mortality in adult patients with CM. However, little is known about the frequency and severity of MODS in children with CM. This was a retrospective study of 199 pediatric patients with CM admitted to a referral hospital in Blantyre, Malawi, between January 2019 and May 2023. Data were abstracted from charts to calculate scores using four established scoring systems: Pediatric Logistic Organ Dysfunction-2 (PELOD-2), Pediatric Sequential Organ Failure Assessment (pSOFA), Signs of Inflammation in Children that Can Kill (SICK), and Lambaréné Organ Dysfunction Score (LODS). Mortality was 16% (n = 32). All four scoring systems were predictive of mortality, but the PELOD-2 and pSOFA scores outperformed the others with area under the curve values of 0.75 and 0.67, respectively. Multiple organ dysfunction syndrome was diagnosed in 182 patients (91%) using the PELOD-2 score, 172 patients (86%) using the pSOFA score, 99 patients (50%) using the SICK score, and 30 patients (15%) using the LODS. The PELOD-2 and pSOFA identify MODS in children with CM but require laboratory-based testing that is often unavailable in malaria-endemic areas. Furthermore, these scoring systems may identify primary malarial disease pathology rather than true organ dysfunction. Simplified scoring systems designed to recognize and quantify MODS in this patient population may provide opportunities for improved resource allocation and timely, organ-specific treatment.