Based on our experience, monitoring of children with immunosuppression and COVID-19 disease can be performed as outpatients, if close monitoring is possible with radiological and blood test controls if necessary, and carefully selecting the patients depending on their individual risk. Hospitalization should be assessed when high fever, radiological involvement, and/or respiratory distress is present. Also, it should be considered if there are signs of disease severity (lymphopenia, elevated D-dimer, C-reactive protein or Interleukin-6). Depending on the evolution, an sHLH must be ruled out. A judicious and conservative treatment seems safe and recommended since to date no antiviral treatment has shown efficacy. It is particularly relevant to be very careful when recommending any specific antiviral treatment in this group of patients given the numerous drug interactions that may appear with their immunosuppressive treatment, such as calcineurin inhibitors, among others. The available tables of pharmacological interactions should always be consulted.