Asthma imposes a crucial economic burden on health systems, especially with the incorporation of new drugs. Recently, mepolizumab has been approved to prevent exacerbations in patients with eosinophilic asthma. This study explores the economically justifiable price of mepolizumab for preventing exacerbations in children with severe asthma. A model was developed using the microsimulation to estimate the quality-adjusted costs and life years of two interventions: mepolizumab versus not applying standard treatment without mepolizumab. This analysis was made during a time horizon of 50 years and from a third-payer perspective. Mepolizumab was cost-effective using a WTP of U$ 19,992 per QALY, but not at a WTP of U$ 4828, U$ 5128 per QALY. The economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of U$ 4828, and U$ 5128 respectively. At the current price of Mepolizumab, U$ 780 per dose, only using a WTP higher than U$ 10,300 per QALY mepolizumab will be the best alternative to no mepolizumab. Our study shows that the economically justifiable cost for mepolizumab in Colombia is between $33 and $350 per dose, for WTP of 4828 and 5180 respectively. This result should encourage more studies in the region that optimize decision-making processes when incorporating this drug into the health plans of each country.