Introduction: Toxic shock syndromes (TSS) are severe shocks due to staphylococcal or streptococcal infection that require specific treatments. The early recognition of these shocks is crucial to improve their outcomes.Objectives: The primary objective of this study was to compare characteristics and outcomes of staphylococcal and streptococcal TSS in children, in order to identify putative early clinical diagnostic criteria. Secondary objectives were to determine the toxin gene profiles of associated isolated strains and the relevance of measuring Vβ T-cell signatures to confirm the diagnosis.Study design: We performed a multicenter retrospective evaluation of clinical data, biological results, and treatment outcomes of children with a confirmed or probable case of staphylococcal or streptococcal TSS. Children were consecutively included if they were admitted to the pediatric intensive care units of Lyon (France), between January 2005 and July 2011.Results: Among the 30 analyzed children, 15 presented staphylococcal TSS and 15 streptococcal TSS. The most frequent origin of staphylococcal and streptococcal TSS was the lower respiratory tract (53%) and the genital tract (47%) respectively. Non-menstrual TSS syndrome cases presented more frequently with neurological alterations, and digestive signs were predominant in menstrual forms. Compared to Staphylococcal TSS, Streptococcal TSS presented with higher organ dysfunction scores (median Pediatric Index of Mortality 2 score 20.9 (4.1–100) vs. 1.7 (1.3–2.3), p = 0.001), required respiratory support more frequently (80 vs. 33%, p = 0.02), were intubated for a longer time (3 days (0.75–5) vs. 1 day (0–1.5), p = 0.006) and had a non-significant trend of higher, case-fatality rate (20 vs. 7%, p = 0.60). The lack of antitoxin therapy was associated with higher case-fatality rate (50 vs. 4%, p = 0.04). The Vβ repertoire measurements exhibited toxin dependent-alterations in accordance with the toxin gene profiles of isolated strains in both types of toxic shock syndromes. Regarding toxin gene profiles of isolated strains, 10/15 Staphylococcus aureus belonged to clonal complex (CC) 30 and 6/12 Streptococcus pyogenes were emm1 type suggesting clonal etiologies for both staphylococcal and streptococcal TSS.Conclusion: Despite the involvement of functionally similar toxins, staphylococcal and streptococcal TSS differed by their clinical signs, origin of infection and prognosis. The detection of Vβ profiles was useful to confirm the diagnosis of staphylococcal and streptococcal TSS and for the identification of involved toxins.