Serological diagnostic methods (anti-T. gondii IgM and IgG) and PCR-based diagnosis are the two main methods used to diagnose acute toxoplasmosis. However, serological assays pose limitations, such as IgM false positives, the long-lasting presence of residual specific Abs, and potential IgG immaturity, complicating diagnostic decision making. Moreover, PCR-based diagnosis is not always useful in the case of acute acquired toxoplasmosis. T. gondii excretory-secretory Ags (ESAs) form the majority of the circulating Ags (CAgs) present in serum of patients with acute toxoplasmosis and have been proven to be useful and valuable for acute toxoplasmosis diagnosis. Additionally, the infection route has no effect on the detection of CAgs. Particularly, they have been shown to exist in the cerebrospinal fluid of HIV-infected patients with cerebral toxoplasmosis. Thus, screening and identification of diagnostic markers from CAg components can therefore help to improve the accuracy of acute toxoplasmosis diagnosis.