Background: More than 200 diseases can be represented in differential diagnosis of fever of unknown origin (FUO). The mainstay for the proper diagnosis of FUO took right path for the correct investigations. Globally, Toxoplasma gondii infection persists lifelong within the affected host organs in the dormant bradyzoites form. Once the host immunity decreases, it can be converted back to the activate tachyzoite form that attach the host cells. Aim: The aim of our study is to estimate the frequency of toxoplasmosis in patients with fever of unknown origin, concerning the aetiology. Methodology: A cross-sectional study was done from November 2017 to May 2018, including 140 patients chosen with FUO (100 males &40 females), recruited from Port Said Fever Hospital/ Egypt. Their ages ranged between 16 and 70 years old. Patients were subjected to comprehensive history taking, laboratory investigations, clinical and radiologic examination. Detection of anti-Toxoplasma IgM & IgG antibodies was done by the Electrochemiluminescence immunoassay. Patients had fever with known origin proved by investigations, were excluded from the study. Results: The results showed that 7.1% of the FUO cases were serologically positive for Toxoplasma IgG. Of them, 80% were females and 20% were males. About 70% of Toxoplasma-IgG positive cases were represented with fever for 3weeks, and 30% were represented with fever for more than 3weeks. The 70% of the target group had cervical lymphadenopathy and all of them had hepatosplenomegaly. Moreover, all cases were eating fast food.