Toxoplasma gondii is associated with physiological and psychiatric perturbations. The immune response is interrelated to the progress of anhedonia and despair symptoms of T. gondii-infected subjects. We recently reported that serum N-glycans were altered in mice displayed depressive-like behaviors. However, a novel biomarker that correlated to T. gondii infection and associated behaviors is demanded. Glycomics has been used to find affected glycoproteins during depression. The objective of this study is to investigate serum N-glycomics changes during infection with T. gondii in BALB/c mice, immunocompetent, or in severe combined immunodeficient mice, and after treatment with an immunostimulant; 1-methyl tryptophan. Glycans were examined through glycoblotting-protocol then investigated by MALDI-TOF/MS. Both depressive and sickness-related behaviors were significantly abundant (P ≤ 0.001 each), during acute T. gondii in immunocompetent mice, compared to controls. Only sickness symptoms were evident in immunodeficient mice infected with T. gondii, as associated with high expression level (P ≤ 0.001) of Peak # 15 (2 × Neu5Gc) compared to controls. The alteration of sialylated N-glycan expressions is important to detect the immune status of animals/humans against T. gondii. Moreover, 1-methyl tryptophan reduced depressive-like behavior (P ≤ 0.001) compared to controls. Therefore, sialylated N-glycan (Neu5Ac/Neu5Gc-terminal) is targeted to be used as a novel biomarker of sickness/depressive-like behaviors.