Objective: To describe the clinical characteristics of invasive Staphylococcus aureus infections in children and identify the prognostic factors of severity and mortality. Materials and methods: Observational study in patients < 16 years old hospitalized between 2010 and 2015 due to invasive S. aureus infections at the Instituto de Medicina Tropical, in Asunción, Paraguay. Patients were distributed based on whether or not they required admission to the intensive care unit, and clinical, laboratory, and evolutionary outcome measures were compared. Results: Out of the 107 included patients, 50 (47 %) developed bacteremia; 50 (47 %), pneumonia; and 21 (19 %), multifocal disease. Among the patients who were admitted to the intensive care unit (41 %), prior antibiotic use (p < 0.05), the presence of bacteremia (p = 0.01), the presence of comorbidities (p < 0.05), and multifocal disease (p < 0.01) were more frequent. The overall mortality rate was 15 %. The mortality-associated risk factors were the presence, at the time of admission, of hypotension (p < 0.01), multifocal disease (p < 0.01), bacteremia (p < 0.01), leukopenia (p < 0.01), severe anemia (p < 0.01), and metabolic acidosis (p < 0.01), among others. Conclusions: The prognostic factors of severity included prior antibiotic use, bacteremia, the presence of comorbidities, and presentation with multifocal disease. Mortality was significant; associated risk factors included the presence, at the time of admission, of hypotension, multifocal disease, leukopenia, severe anemia, and metabolic acidosis.