Systemic lupus erythematosus (SLE) is an autoimmune disorder of the multisystem, a multifactorial disease with generalized persistent inflammation that can involve multiple tissues and organs. Nucleosomes are essential chromatin molecules, and are thought to be the main antigens in SLE pathogenesis. A case-control study was performed to show the relationship between antinucleosome antibodies and systemic lupus erythematosus in Najaf province. This study was carried out in the Department of Microbiology in the Faculty of Medicine- University of Kufa, for the period of (January 2018 to December 2018), subjects were included in present study, divided into three groups: SLE patient (30), RA patient (30), and Healthy controls(20). Anti-NCS antibodies, ANA and anti-dsDNA antibodies were done for all individuals those included in this study. The findings of the current study showed that, in sera of SLE patients the mean level of antibodies against the following parameters NCS, ANA and ds-DNA were high in comparison with the mean levels of these parameters in sera of the normal control group (p<0.001). As well as, the levels of antibodies against NCS significantly higher in sera of the SLE group than in the rheumatoid arthritis RA (diseased control group) (p<0.001). On the other hand, the mean levels of antibodies against NCS were statically insignificant (p value 0.356) among the healthy individuals and the diseased control group. Anti-NCS antibodies have an important role in SLE diagnosis in comparison to other autoantibodies, and may have a role to predict the disease outcome.