Background: Systemic lupus erythematosus (SLE) is a chronic connective tissue disease with multisystem inflammation, complement system aid in deposition of immune complexes. Hydrolyzing phosphatidylserine on the plasma membrane of apoptotic cells and activating neighboring immune cells by producing lysophospholipid, phospholipase A1 promotes the onset of autoimmunity in SLE patients. Objective: To determine the levels of Phosphatidyl Serine-Specific Phospholipase A1 (PS-PLA1), and the total hemolytic complement in the sera of SLE (CH50) patients and to clarify how these levels correspond to the severity and activity of the disease. Patients and methods: 80 persons participated in the study (40 SLE patients and 40 healthy as control group). The disease activity level is evaluated as regards the SLE disease activity score, laboratory tests and enzyme linked immune-sorbent test for Phosphatidyl Serine-Specific Phospholipase A1 and the total hemolytic complement. Results: This study revealed a significant difference in PS-PLA1 and CH50 levels in the patient group when compared to healthy patients. The values of (SLEDAI) and laboratory parameters including antinuclear-antibody, anti-double stranded, erythrocyte sedimentation rate, CBC, and albumin/creatinine ratio levels were significantly associated with PS-PLA1, and CH50 in SLE patients (P< 0.05). Conclusion: Sequential changes of PS-PLA1, and CH50 concentrations in SLE patients and a strong correlation existed between SLEDAI with both markers, suggesting their putative role in the disease pathophysiology.