Background: Systemic lupus erythematosus (SLE) is an autoimmune disease, characterized by autoantibody production and immunocomplex formation, leading to widespread inflammatory damage involving multi-organ systems. Lymphopenia is a common laboratory involvement seen in patients with SLE and the mechanism of it is still unclear. Objectives: The aim of the current study was to investigate the relation between lymphopenia and clinical manifestations, laboratory findings, and disease activity in systemic lupus erythematosus (SLE) patients. Patients and Methods: It was a cross sectional study; with a total of 60 patients with SLE recruited from the Rheumatology and Rehabilitation outpatient clinic at Sohag University Hospital. Demographic data, personal history, detailed history of general health condition and chronic or current diseases were reported. All the participants were subjected to detection of erythrocyte sedimentation rate, liver function tests, renal function tests, complete blood count (CBC), renal biopsy, protein/creatinine ratio and/or 24hr protein in urine, urine analysis, ANA profile, and Complement 3 and 4. Results: Two thirds of the study population had normal lymphocytic count, and one third had lymphopenia. Lymphopenia group showed significantly more hypochromic anemia with significant lower hemoglobin level and lower MCV. The mean creatinine level was significantly higher among lymphopenic cases. Lymphopenic cases had higher proteinuria. Conclusions: It could be concluded that lymphopenia in patients with SLE may be used as indicator of renal involvement in these patients.