Abstract Objective To ascertain a relationship between Toxoplasma gondii (T. gondii) infection and rheumatoid arthritis (RA) disease among Egyptian patients. Methods One hundred RA patients and 50 healthy subjects participated in this study. The patients were classified into three groups, namely GI, G2 and G3. Patients in G1 were recently diagnosed with RA with the disease duration of less than one year (prior treatment); G2 included RA patients receiving anti-tumor necrosis factor agents and RA patients in G3 received disease modifying anti-rheumatic drugs (methotrexate, antimalarial, corticosteroids). Serum samples of all participants were examined for the presence of anti-Toxoplasma immunoglobulin G (IgG) antibodies and positive samples were further analyzed for anti-Toxoplasma IgM antibodies to detect the possibility of reactivation of latent toxoplasmosis. Also, the association between Toxoplasma seropositivity and clinical, laboratory and radiological features of these patients were determined. Results There was a significantly higher percentage of T. gondii IgG positivity in RA patients (54%) than in the controls (32%). At the same time, 20.40% of T. gondii IgG positive patients had anti-T. gondii IgM antibodies with a statistically significant difference as comparing to T. gondii IgG positive controls. Out of T. gondii seropositive patients, 20.37% had a lower IgG level with a mean titer of (65.3 ± 17.7) IU/mL, 46.29% had moderate level with a mean titer of (184.2 ± 60.0) IU/mL and 33.33% had higher level with a mean titer of (404.3 ± 50.0) IU/mL. A positive correlation was found between disease activity and Toxoplasma seropositivity. T. gondii seropositive RA patients had longer disease duration, longer time morning stiffness, higher numbers of tender and swollen joints and also increase in disease severity markers (erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, anti-cyclic citrullinated peptide anti-bodies, rheumatoid factor) than T. gondii seronegative patients. As regards radiological findings, Larsen score was found significantly higher in T. gondii seropositive RA patients. Conclusions The positive correlation between T. gondii infection and RA disease among Egyptian patients indicated the need to improve awareness of this parasitic infection and its management in this risk group.