The objective of the study is to study the positivity of Coombs test or direct antiglobulin test (DAT) in systemic lupus erythematosus (SLE) patients and its relationship with disease's clinical and serological profile. Retrospective study of 373 SLE patients seen at single Rheumatology Unit. Epidemiological data (age, gender, age at disease onset, auto declared ethnic background and tobacco use), clinical (malar rash, photosensitivity, oral ulcers, discoid lesions, serositis, glomerulonephritis, convulsions, psychosis, hemolytic anemia, leukopenia, lymphocytopenia and arthritis), and serological profile (anti ds DNA, anti Ro/SS-A; anti La/SS-B, Anti RNP, Anti Sm, aCl (anticardiolipin) IgG, aCl Ig M, LA or lupus anticoagulant, rheumatoid factor and direct Coombs) were collected. Patients with a positive DAT were compared with the negatives. DAT was positive in 12.8% of patients and 54.3% of them had hemolytic anemia. In univariate analysis, a positive DAT was associated with hemolytic anemia (p < 0.0001), secondary antiphospholipid antibody syndrome (p = 0.02), anticardiolipin IgG (p < 0.0001), lupus anticoagulant (p = 0.05), positive VDRL (p = 0.004), anti-RNP (p < 0.0001), anti-Sm (p = 0.002), and anti-La (p = 0.02). Logistic regression revealed that hemolytic anemia, anti-RNP and anti-LA were independently associated with positive DAT. DAT was positive in 12.8% of SLE studied sample and 54.3% of them had hemolytic anemia. This test was independently associated with hemolytic anemia, anti-RNP and anti-La antibodies.