Summary Objectives Detailed understanding of tuberculosis (TB) immunopathology and cytokine/chemokine responses can ultimately lead to the development of new diagnostic tools, especially useful in children where TB diagnosis remains challenging. Methods Nineteen cytokine/chemokine responses to Mycobacterium tuberculosis (M.tb) antigens were analyzed in 47 children distributed as follow: 28 with TB-disease (TD), 12 with latent TB and 7 uninfected controls. All the cytokines and chemokines were quantified in a multiplexed microsphere-based assay by using residual plasma from the quantiFERON kit (IFNγ release assay). Results IP-10, IL-2, IL-5 and IL-13 were among the best cytokines to diagnose infection as related by the area under ROC curve for IP-10 (0.96, 95%CI: 0.91–1.00), IL-2 (0.98, 95%CI: 0.93–1.02), IL-5 (0.91, 95%CI: 0.81–1.01) and IL-13 (0.97, 95%CI: 0.93–1.00). None of the 5 biomarkers, however, discriminated TB-disease from latent-TB. Finally, lower IL-5 ( p = 0.02) and IL-13 ( p = 0.02) levels were observed in severe opposed to non-severe TB. Conclusion These results suggest that IP-10, IL-2, IL-5 and IL-13 may find a diagnostic application in pediatric tuberculosis and argue against the paradigm of a negative influence of Th2 responses in severe pediatric M.tb infection.