We aimed to determine the rate of varicella infection and complications in children with disorders of intermediary metabolism (IEMs) between the ages of 1 and 16 years attending our national metabolic referral centre. Of 126 children identified, a response was received from 122. A history of previous varicella infection was identified in 64 cases (53%) and of varicella vaccination in 5(4%). Fifty-three (43%) patients apparently did not have a history of clinical varicella infection. Of the 64 children with a history of varicella infection, 5 required hospitalization for complications including life-threatening lactic acidosis in one patient with mitochondrial disease, and metabolic decompensation in 4 patients. In conclusion, varicella infection may cause an increased risk of metabolic decompensation in patients with IEMs.We propose that a trial of varicella vaccination is considered for this cohort of patients with monitoring of its safety and efficacy.