Aim: Asthma affects millions of people worldwide and generates a considerable economic impact. This study aims to compare the specific immunoglobulin E (sIgE) profile in sensitized children with severe asthma from two countries with great geographic and climatic differences. Methods: A cross-sectional study was performed using serum samples analysed with a multiplex tool in 47 children from Sweden and 29 children from Spain. Results: Patients from Spain were significantly more often sensitized to house dust mites, cockroaches, dogs, Alternaria, Cladosporium, pollen from olive trees, cypress, Platanus, and Parietaria, and to Anisakis and shrimp. Swedish patients were significantly more often sensitized to cats, pollen from birch, hazel, and Alnus, and to apple, soy, and peanut (all P < 0.05). With regard to sensitization to allergen molecules, lipid transfer proteins (LTPs), cross-reactive carbohydrate determinant (CCD)-bearing proteins and tropomyosins were more frequent in Spain, while sensitization to pathogenesis-related class 10 proteins (PR-10) molecules and to peanut storage proteins were more common in Sweden. Conclusions: The immunoglobulin E (IgE) profile in sensitized children with severe asthma differed greatly between Sweden and Spain. The profile results were more similar to that reported in the literature for other sensitized children from the same geographic areas with non-severe disease than to that of severe asthmatics from different areas.