Lupus anticoagulant (LA) and beta2-glikoprotein I (b2GPI) dependent anti-cardiolipin (aCL) are part of the diagnostic criteria both of systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS). Anti-phospholipid antibodies (aPL) may also bind to other phospholipids and/or protein co-factors. In the present study, besides aCL and anti-b2GPI, antibodies directed against phosphatidylserine, prothrombin (PT) and annexin V (aANX) were measured in 85 randomly selected SLE patients, 14 suffering from secondary APS. LA was detected by hemostasis tests. Correlations were determined between rare aPLs and clinical manifestations, including thrombotic events. Anti-cardiolipin IgG was positive in 14 patients, aCL IgM in 8, anti-b2GPI IgG in 4 and IgM in 5 patients. LA was detected in nine cases. Seven patients were positive for anti-phosphatidylserine (aPS) IgG, nine for aPS IgM, while anti-PT (aPT) IgG was positive in nine cases. aPT IgM and anti-aANX were negative in all patients. Correlation was found between aPS and aCL antibodies. The frequency and concentration of rare anti-phospholipid/co-factor antibodies was higher in patients with secondary APS. The presence of such rare aPLs cumulated in APS patients, their presence increased the frequency of thrombotic events in the entire study population, furthermore in patients positive for LA or aCL. Rare anti-phospholipid/co-factor antibodies were found in 12% of an un-selected lupus patient population. Their presence was more frequent in patients with secondary APS, and further increased the risk of thrombotic complications.