EPOS 2012 states that investigation is needed to study a possible role for food allergy in the initiation and perpetuation of chronic rhinosinusitis with nasal polyps (CRSwNP). Our main goal was to compare serum levels of food-specific immunoglobulin G (IgG) and IgE antibodies in patients with CRSwNP and controls. A prospective case–control study with 33 patients with CRSwNP and 31 controls without CRS was carried out. Clinical data were gathered through a systematic interview and blood sample was collected. Enzyme-linked immunosorbent assay tests using OmegaDiagnostics kit with 40 food allergens for detection of specific IgG antibodies were performed and food-specific IgE antibodies were determined by immunoassay using ImmunoCAP. Immunoglobulin classes and IgG subclasses levels were also evaluated. Statistical analysis was performed using SPSS v.23. The overall sum of food IgG antibodies was significantly lower in CRSwNP compared to control group, and this difference was also observed for different specific IgG antibodies (corn, soya, grain legumes, pear and apple, berries, citric fruit). In controls, a positive correlation between IgG1 and the sum of food IgG antibodies was seen, but in CRSwNP group a negative correlation was found. In addition, a significant higher level of IgG1 and lower IgG2 and IgG3 was found among patients with CRSwNP. Levels of serum-specific IgE antibodies against multiallergen food mix (fx5) and against shrimp, strawberry, orange, rye, or egg yolk, as well as the sum of food IgE antibodies, did not differ significantly between the groups. These findings suggest that food allergy does not have an important role in CRSwNP etiopathogenesis, whether it is IgG or IgE mediated. Moreover, the observed suppression of specific IgG antibodies against food allergens, its negative correlation with IgG1 and the IgG1 switching in CRSwNP, can be related to deviated IgG responses against other targets (eg, airborne particles) and warrants future investigation.