Abstract The febrile illness caused by dengue is a global public health problem whose incidence is increasing. This infection can range from mild fever to severe illness with plasma leakage and shock; therefore, biomarkers of severity are urgently needed to elucidate the pathological mechanism of the disease. To explore the levels of interleukin (IL)-10 and interferon (IFN)-β in children with dengue to identify these proteins as biomarkers of severity. This study compared the serum levels of IL-10 and IFN-β in 208 Colombian paediatric patients with different degrees of severity of dengue virus infection. A total of three study groups (dengue without warning signs, dengue with warning signs, and severe dengue) were designated according to the World Health Organization classification system. Serotype type 2 was the most prevalent type, and the most frequently reported symptom was vomiting, followed by abdominal pain. Platelet values, aspartate transaminase and alanine transaminase levels and clotting times were the most altered laboratory parameters among the study groups and were more pathological in patients with severe dengue. In addition, IL-10 levels were significantly higher in those with severe dengue than in those with milder forms of infection (P < .05), and IFN-β levels were much lower in the group of patients with severe dengue than in the group with dengue without warning signs (P < .05). These results demonstrate differences in immune responses to dengue infections and suggest several molecular targets for the future development of biomarkers that can serve as diagnostic and prognostic tools for the severity of dengue disease.