Background: Eosinophilic asthma (EA) is characterized by abnormal production and release of type 2 cytokines, such as interleukin-5 (IL-5), from T helper type 2 (Th2) lymphocytes and type 2 innate lymphoid cells (1). The aim of this study was to evaluate the usefulness of the basophil phenotype assessment and serum IL-5 assay in monitoring a series of severe EA patients treated with anti IL-5 drugs and correlate the results of these tests with baseline patients’ characteristics and clinical response, with particular attention to systemic steroid use and asthma exacerbations. Methods: Blood samples of 19 severe asthma patients were collected at T3 and T6 for evaluation of serum levels of IL-5 and basophil phenotype assessment. Results: All patients experienced an improvement of lung function, with an increase of FEV1 from a mean value of 71.9 to 83.8% of the theoretical value (+12%). Oral corticosteroids were progressively reduced and finally stopped in 14 (73.7%) of the 19 patients after six months of follow-up. Patients who achieved a complete response to anti-IL5 treatment showed a rate of activated basophils CD3negCRTH2posCD203cposCD125pos (4.78 ± 2.26%) at T0 significantly lower than that of patients not achieving the complete response (34.57 ± 14.01%, p=0.05). Conclusions: This pilot study in EA patients shows that the determination of activated basophils, that express CD125 is related to anti IL5/IL5Rα drug mechanism of action and subsequent immune response, proving to be a biomarker that identifies the patient’s phenotype that responds to therapy and that requires the concomitant use of OCS.