Objectives: This study will investigate olanzapine’s cytogenetic behavior in cultured human T lymphocytes in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Methods: Three olanzapine solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides and stained with the fluorescence plus Giemsa method. Sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope.Results: There was a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE and RA patients compared to healthy individuals and a statistically significant (p=0.001) reduction of PRI and MI in the highest concentration in the SLE group. Moreover, Spearman's rank correlation coefficient was applied to calculate the correlation between SCEs, PRI, and MI. Negative significant correlations were noticed for both patient groups concerning SCEs-PRI alterations and SCEs-MI alterations. Conversely, positive correlations were noticed for both patient groups for PRI-MI alterations.Conclusions: Olanzapine affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures and DNA damage response. Considering the use of olanzapine in neuropsychiatric symptoms of SLE, further in vivo studies are necessary to evaluate its effect on human DNA.