Background: Medically unexplained symptoms commonly present to pediatricians with no apparent cause following extensive investigations. Such patients frequently present with multiple chronic symptoms including memory problems, insomnia, dizziness, digestive problems and variable somatic complaints such as headache and muscle pain. Objective: This study aims to characterize the symptom profile of children presenting with multiple medically unexplained symptoms. We hypothesize that these symptoms reflect a maladaptive stress response and dysregulated nervous system due to chronic stress following a trauma event. Methods: Study patients were identified from a university-based weekly outpatient Child Neurology clinic between June to September 2015. Patients were included if they were >2 years of age, with >/= 4 medically unexplained symptoms. Children with developmental delay were excluded. Symptoms were grouped under the following categories: 1) executive dysfunction, 2) sleep disturbance, 3) autonomic dysfunction, 4) somatization, 5) digestive problems, and 6) emotional dysregulation. Trauma history was obtained from a detailed social history in all patients. Results: Out of 100 consecutive patients, 17 were included; 12 females, median age 14 years (range 5-17 years). All patients experienced at least one symptom in each of the following categories: sleep disturbance, autonomic dysfunction, somatization and emotional dysregulation, while 82% exhibited executive dysfunction, and 59% had digestive problems. Fifteen patients (88%) disclosed a history of trauma including domestic violence, parental substance abuse, physical or sexual abuse, bullying, or medical trauma, compared to 17% of controls (p < 0.0001). Conclusions: In a consecutive cohort of patients from a university-based outpatient Child Neurology clinic, children with multiple medically unexplained symptoms accounted for 17% of the clinic population. We propose the term “nervous system dysregulation” to describe children with multiple medically unexplained symptoms involving at least one symptom in each category of 1) sleep disruption, 2) autonomic dysfunction, 3) somatization, and 4) emotional dysregulation. Children with this symptom profile are likely to have a history of traumatic events, suggesting that symptoms may arise from chronic activation of the physiological stress response system. Nervous system dysregulation should alert the physician to a possible history of psychological trauma as a cause for symptoms to reduce the morbidity associated with unnecessary medical procedures, and pursue appropriate therapy.