The peptide trefoil factor family 3 (TFF3) is a major constituent of the intestinal mucus, playing an important role in the repair of epithelial surfaces. To further understand the role of TFF3 in the protection of intestinal epithelium, we tested the influence of TFF3 in a murine Toxoplasma gondii-induced ileitis model. Surprisingly, TFF3KO mice showed a reduced immune response in the ileum when compared to wild-type animals. Interleukin-12 and interferon-γ expression levels as well as the number of CD4+ lymphocytes were reduced in the infected TFF3KO mice. These effects were in line with the trend of elevated parasite levels in the ileum. Moreover, TFF1 expression was upregulated in the spleen of infected mice. These initial results indicate that TFF3 is involved in the immune pathology of T. gondii infection-induced intestinal inflammation. Thus far, the mechanisms of how TFF3 influences the immune response are not fully understood. Further studies should identify if TFF3 affects mucus sensing of dendritic cells and how TFF3 is involved in regulating the immune response as an intrinsic secretory peptide of immune cells.