Background: the relationship between neuropsychiatric manifestations and systemic lupus erythematosus (SLE) reactive autoantibodies is controversial and was not investigated before in Sudanese psychiatric patients. Aim: to determine the association between psychiatric manifestations and several SLE reactive autoantibodies regardless of the presence of other SLE manifestations. Material and Methods: the study involved a test group of one hundred psychiatric patients and age/gender matched control group of one hundred apparently healthy subjects. Antinuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA) antibodies and ANA profile3 concentrations were measured for each studied subject using ELISA method. The association between various SLE reactive antibodies and psychiatric illnesses were assessed using Mid-P extract test. P < 0.05 was considered significant. Results: all subjects in the control group were ANA and dsDNA negative, however, only one (1%) was positive for anti-histone antibody (ANA profile3). Regarding patients with psychiatric diseases, 6% were ANA positive, 2% were dsDNA and 6% ANA profile3 positive. In contrast to dsDNA, there were significant associations between psychiatric diseases and ANA and/or ANA profile3 antibodies (P = 0.007 for ANA, P = 0.0.125 for dsDNA and P = 0.033 for ANA profile3). Conclusion: Sudanese patients with psychiatric diseases tend to have positive SLE reactive autoantibodies especially for ANA and ANA profile3 antibodies.