Introduction:Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are two autoimmune disorders that can develop together or separately. Similarities in the pathogenesis have been discovered, including the production of autoantibodies that target subcellular antigens and shared elevated risk of cardiovascular morbidity, which may be caused by common pathologic pathways.Case presentation:A 28-year-old male, referred to our hospital for the assessment of chest pain. Past medical history was significant for extensive deep venous thrombosis despite the appropriate management with a therapeutic dose of direct-acting oral anticoagulant. Prolonged partial thromboplastin time was not corrected by mixing study along with positive lupus anticoagulant, anticardiolipin, and B-2 glycoprotein antibodies. In addition, antinuclear antibodies, anti-DNA antibodies, and direct Coombs were positive with decreased levels of C3. The patient was diagnosed with SLE with brain, heart, and kidney involvement in the setting of antiphospholipid antibody syndrome. He was treated successfully with full recovery.Discussion:SLE and APS both have sneaky ways of manifestation. Ineffective diagnosis and therapy could cause irreversible organ damage. Clinicians should have a high index of suspicion for APS, particularly in young patients who approach with spontaneous or unprovoked thromboses or unexplained recurrent early or late pregnancy loss. Anticoagulation, modifying cardiovascular risk factors, and identifying and treating any underlying inflammatory diseases are all part of the multidisciplinary care that is needed for management.Conclusion:Although male affection is rare, SLE and APS should be considered in male patients as these conditions tend to be more aggressive than in the female.