Background: Corticosteroids as modulation the inflammatory response is a controversial issue in the treatment of bronchiolitis. This study aimed to assess whether corticoid therapy influenced the inflammatory and clinical response of critically ill infants. Methods: Prospective, randomized, double blind placebo-controlled trial of glucocorticoids (GCT) in infants of less than 12 months with severe or moderate bronchiolitis. Patients were randomized to receive corticoid therapy or placebo. The main outcomes were: a) levels of lymphocyte; b) levels of IL-2, IL-12, and IFNγ as pro-inflammatory factors, and c) levels of IL-4 and IL-10 as anti-inflammatory response. Secondary outcomes related with the clinical response were also analyzed. Results: 97 patients were randomized. Evolution of lymphocyte subsets was similar in both groups. Pro-inflammatory interleukins and interferon decreased, but without differences. Antiinflammatory interleukins showed a significant decrease from baseline to the end of the study, and IL-10 values were significantly lower in the GCT group. GCT group showed a lower time of mechanical ventilation and of hospitalization, but without statistically significant differences No cases of severe adverse reaction to steroids were detected. Conclusions: administration of systemic GCT did not modify the inflammatory not the clinical response of patients with severe bronchiolitis, except for IL-10 levels that were significantly lower in the GCT group. Trial registration: Glucocorticoid Therapy Impact on the Inflammatory Response and Clinical Evolution in Patients With Severe Bronchiolitis, NCT02571517. ClinicalTrials.gov registration number: 2011-000337-36. Date of registration: 30 june 2012 (retrospectively registered).