BACKGROUND: Mepolizumab, an IL-5 receptor antagonist, is a targeted therapy approved for treating severe eosinophilic persistent asthma. While it offers significant clinical benefits in reducing exacerbations and improving quality of life, its high cost raises concerns about its affordability and overall value in resource-constrained settings. This study evaluates the cost-effectiveness of adding mepolizumab to standard care (SoC) compared to SoC alone in adolescents and adults with severe, uncontrolled eosinophilic asthma in Colombia. METHODS: We used a Markov model with a societal perspective and a lifetime horizon to estimate costs and quality-adjusted life years (QALYs). Parameters were derived from local data and existing literature. Both deterministic and probabilistic sensitivity analyses were performed to test the model's robustness. Cost-effectiveness was assessed using a willingness-to-pay threshold of US,130. RESULTS: Mepolizumab demonstrated an additional 0.31 QALYs per patient compared to standard of care (SoC), with an incremental cost-effectiveness ratio (ICER) of US5,210 per QALY gained. Sensitivity analyses showed that the price of mepolizumab was the key driver of cost-effectiveness. Over a 5-year horizon, adding mepolizumab to SoC would have a significant budgetary impact. These findings highlight the need to balance clinical benefit with affordability in resource-limited settings. CONCLUSION: Although mepolizumab improves patients' quality of life, it is not considered cost-effective in Colombia under the conditions of this study. The results provide valuable information for policymakers to consider when refining local clinical practice guidelines.