During the last year, severe acute hepatitis of unknown origin has presented the maximum peak of appearance in previously healthy children under 16 years of age, exceeding 800 reported cases. The frequent clinical manifestations are of gastrointestinal origin, with jaundice and elevated liver enzymes being the main findings discussed. Routine paraclinical tests show negative results for infection with common hepatotrophic viruses such as hepatitis AE, therefore, currently, the main etiological suspicion is redirected to the presence of human adenovirus serotype 41 or to the activation of immune cells mediated by SARS superantigens -CoV-2.