Background: Acquired thrombotic thrombocytopenic purpura (TTP) is a rare disease. In middle and low-income countries, specific resources are required for its diagnosis due to the lack of diagnostic tests and the variable response to plasma exchange, especially in the context of the new SARS-CoV-2 pandemic. Case report: We report the case of a 9-year-old male Hispanic patient with SARS-CoV-2 infection, atypical presentation, and multisystem involvement, thrombotic microangiopathy with dermal manifestations, hematologic, renal, and neurologic involvement. The patient was followed up after SARS-CoV-2 infection, the PLASMIC score was applied, and a genetic study was performed. Ventilation and hemodynamic support, corticotherapy, immunoglobulins, plasma exchange, renal replacement therapy, and monoclonal antibodies were given without favorable response. Conclusions: TTP associated with SARS-CoV-2 in the pediatric population is rare. However, resources for the diagnosis, support, and management of patients with TTP are required to avoid fatal outcomes.