The etiology of Crohn's disease (CD) is still unknown although new theories are based on defects in innate immunity. We have previously shown a decrease in gamma delta T cells in CD patients. Previous studies have shown a high prevalence of anti-A. simplex immunoglobulins in CD patients. The diminution of gamma delta T cells in the peripheral blood and intestinal mucosa of CD patients may create a state of immunosuppression that would facilitate A. simplex infection. To study the antibody responses to Anisakis antigens in Crohn's disease patients and its relationship with alpha beta and gamma delta T cell subsets. We recruited 81 CD patients and 81 healthy controls. alpha beta and gamma delta T cell subsets and anti-A. simplex antibodies were measured. Levels of anti-A. simplex IgG and IgM were significantly increased in CD patients. Almost 20% of CD patients were positive for IgG and IgM anti-A. simplex versus only 3.7 and 2.5%, respectively, in normal subjects. However, lower specific IgA levels were observed in the group of CD patients versus healthy subjects. We found an association between CD3 + CD8 + gamma delta subset and IgM anti-A. simplex levels. In ileal cases and stricturing behavior of CD, we observed the highest levels of specific antibodies with the exception of anti-A. simplex IgA. The relationship of specific antibodies with a gamma delta T cell deficiency makes these cell candidates to play a role in the immune response against Anisakis. In addition, anti-Anisakis antibodies could be considered as markers of risk of progression in CD.