Background: Lupus erythematosus is a diverse autoimmune disorder that is capable of afflicting a variety of organs and has a clinical history that is inconsistent. Despite substantial improvements in systemic lupus erythematosus (SLE) patient survival, the pathophysiology of the disease remains unexplained, despite the fact that genes play a key role in its propensity. Objective: To evaluate the several hematological indicators (neutrophil- to- lymphocyte ratio (NLR), platelet -to- lymphocyte ratio (PLR), platelet distribution width (PDW), red cell distribution width (RDW), mean platelet volume (MPV) in SLE patients and their correlation with disease manifestations. Patients and Methods: In our study, a cross-sectional comparative study that enrolled 100 SLE patients (30 male and 70 female patients) aged from 18-55y who are recruited from the Internal Medicine Department, Rheumatology Unit (inpatient wards and outpatient clinics) the patients were categorized into three groups according to the (SLE disease activity index 2000. (SLEDAI-2K): Group (I): Inactive (SLEDAI-2K, Results: Our study showed clinical parameters such as vasculitis, nephritis, serositis, CNS involvement are significant and indicate severe activity. Also, our study showed laboratory data as ESR, ANA, anti-dsDNA, and consumption of complement showed a significant correlation with systemic lupus activity. The highly active group had higher PLR, NLR, PDW, and MPV than other groups. However, the highly active group showed a decrease in lymphocyte median. CNS symptoms indicated a negative correlation that is statistically significant with lymphocytes. While it demonstrated a statistically significant positive correlation, with NLR, however, CNS showed a significant positive correlation with PDW. Nephritis had a significant positive correlation with NLR and PLR. Vasculitis had a positive highly significant correlation with lymphocytes and a positive significant correlation with PLR. Conclusion: Patients with SLE in both high and moderate activity of disease exhibited significant renal manifestations, vasculitis, serositis, CNS symptoms, consumed C3 and C4 while ESR and Anti-dsDNA were elevated in all groups. The highly active group had higher NLR, PLR, PDW, and MPV than other groups. However, it showed a decrease in lymphocyte median. Further, CNS symptoms revealed a negative correlation that is statistically significant with lymphocytes, while it showed a positive statistically significant correlation with PDW and NLR. Nephritis had a positive significant correlation with NLR, and PLR and vasculitis had a positive highly significant correlation with lymphocytes and PLR.