To assess the presence of Mycoplasma pneumoniae-associated encephalitis in children in Switzerland and its likely pathogenesis.M. pneumoniae-associated encephalitis cases seen at a single-centre during 2010-2013 were reviewed, and the Swiss Paediatric Surveillance Unit (SPSU) prospectively conducted a nationwide surveillance 2013-2015. Case definition included confirmed, probable and possible cases.Seven patients (median age 8.7 years, range 4.7-10.1 years) with confirmed or possible M. pneumoniae-associated encephalitis were observed. All patients manifested prodromal respiratory symptoms over at least 5 days and five out of the six who had a chest radiograph, showed pulmonary infiltrates. M. pneumoniae DNA in cerebrospinal fluid was negative in all patients. Intrathecally synthesised M. pneumoniae-specific immunoglobulin (IgM and IgG) were investigated and found positive in one patient (confirmed case). M. pneumoniae DNA in respiratory specimens and/or M. pneumoniae-specific IgM and IgG in serum were detected in the other six patients (possible cases). One confirmed and two possible cases had neurological sequelae at 4-19 months follow-up.The lack of detectable M. pneumoniae DNA in cerebrospinal fluid of our encephalitis patients suggests a likely immune-mediated pathogenesis ignited by a respiratory inflammatory process including pneumonia.