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Background: The mechanism of allergic reactions to COVID-19 mRNA vaccines has not been clarified. Polyethylene glycol (PEG) is a potential antigen in the components of vaccines. However, there is little evidence that allergy after COVID-19 mRNA vaccination is related to PEG. Furthermore, the role of polysorbate (PS) as an antigen has also not been clarified. The objective of this study was to investigate whether PEG and PS allergies are reasonable causes of allergic symptoms after vaccination by detecting PEG-specific and PS-specific antibodies. Methods: Fourteen patients who developed immediate allergic reactions to BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines and nineteen healthy controls who did not present allergic symptoms were recruited. Serum PEG-specific immunoglobulin E (IgE) and immunoglobulin G (IgG) and PS-specific IgE and IgG were measured by enzyme-linked immunosorbent assay. Skin tests using PEG-2000 and PS-80 were applied to five patients and three controls. Results: Serum levels of PEG-specific IgE and IgG in patients with immediate allergic reactions to the COVID-19 mRNA vaccine were higher than those in the control group. Serum levels of PS-specific IgE in patients with allergy to the vaccine were higher than those in patients of the control group. Intradermal tests using PEG verified the results for PEG-specific IgE and IgG. Conclusions: The results suggest that PEG is one of the antigens in the allergy to COVID-19 mRNA vaccines. Cross-reactivity between PEG and PS might be crucial for allergy to the vaccines. PEG-specific IgE and IgG may be useful in diagnosing allergy to COVID-19 mRNA vaccines.