Introduction: Systemic lupus erythematosus (SLE) is a complex systemic autoimmune disease, characterized by immune-mediated inflammation in different organs. The course of the disease is characterized by relapses and remissions, and the degree of severity of the clinical manifestations is greatly affected by the number and nature of the various organ affection. The death rate in patients with SLE is still significant, and it may be due to lupus activity, when vital organs are affected, the complications of treatment especially infections or long-term complications, such as cardiovascular disorders. Objective: To detect the relation between thrombocytopenia in SLE patients and presence antiphospholipid antibodies. Patients and methods: This study was a cross-sectional study included 100 SLE patients who attended to Sohag University Hospitals. Patients included in this study were classified as SLE patients according to either the 2012 SLICC criteria or the new 2017 ACR/EULAR SLE classification criteria. All of the participants were subjected to the following: Full history, full clinical examination, routine investigations, ANA by immunofluorescence, and ANA profile for the most common 19 autoantibodies by immunoblot. All of the participants were subjected to detection of serum titers of all antiphospholipid antibodies (aPLs) including lupus anticoagulant (LA), anti-cardiolipin (aCL) and anti-beta2-glycoprotein I (ab2GPI). Results: In this study, we demonstrated that aPLs are strongly associated with increased risk of thrombocytopenia in SLE patients. We identified aPL profiles, especially LA and IgM isotypes, as biomarkers for the risk stratification of thrombocytopenia in SLE patients. Conclusions: We concluded that aPLs are strongly associated with increased risk of thrombocytopenia in SLE patients.