Background: Cross-reacting carbohydrate determinants (CCD) exist in some pollen and food allergens, but they do not contribute to allergic symptoms. However, CCD can induce specific IgE (sIgE) production and may lead to incorrect allergen diagnosis and treatment. CCD inhibitor is a specific antibody adsorbent which can preclude CCD from binding to sIgE. Currently, the data of CCD inhibition in allergen sIgE test are limited. Methods: The allergic patients with positive skin prick reactions to two or more pollen and/or food allergen extracts were included in our study. Their sera were obtained and sIgE was tested with an allergen panel that included 29 single and mixed allergens (MEDIWISS Analytic GmbH, China) before and after CCD inhibition. The changes of sIgE against these allergens and the correlations of sIgEs to clinical symptoms were analyzed. Results: A total of 44 patients were included and 36 (81.82%) of those were multi-sensitized to house dust mites and pollen allergens based on skin prick tests. The sIgE levels and positive rates against most pollen and food allergens were significantly lower after CCD inhibition. The sIgE levels of pollen were positively correlated to those of food allergens before CCD inhibition. However, these correlations were weakened or no longer existed after CCD inhibition. The sIgE against pollen and food allergens showed significantly higher consistency with clinical symptoms after CCD inhibition. Conclusion: Cross-sensitization caused by CCD is widespread in pollen and food. CCD inhibition test can improve the diagnostic accuracy of pollen and food allergy.