Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that may impact any organ system in the body. Aim: To demonstrate the association between platelet parameters and neutrophil/lymphocyte ratio and SLE disease activity by using the systemic lupus erythematosus disease activity index (SLEDAI) as a disease activity score. Patients and methods: This research has been conducted on 120 cases of systemic lupus erythematosus and 120 controls. The cases were categorized into 60 active lupus patients and 60 inactive lupus patients who were recruited from the internal medicine department of Beni-Suef University Hospital between March 2021 & September 2021. Results: According to the ROC curve, the neutrophil lymphocyte ratio (NLR) showed an AUC of 0.975; the cutoff neutrophil lymphocyte ratio value of >3.5 had 83.3% sensitivity and 100% specificity. Mean platelet volume (MPV) showed an AUC of 0.890; the cutoff MPV value of <8.15 had 83.3% sensitivity and 100% specificity. Platelet distribution width (PDW) showed an AUC of 0.993; the cutoff PDW value of >14.15 had 91.7% sensitivity and 100% specificity. Platelet lymphocyte ratio (PLR): with an AUC of 0.746, the cutoff PDW value of >105 had 66.7% sensitivity and 100% specificity. Conclusion: MPV, PDW, PLR, and NLR can be utilized as inflammatory indicators to assess the severity of SLE in cases. There is an association among them and SLEDAI. Additionally, NLR may indicate kidney involvement in SLE cases, as it is associated with lupus nephritis (LN).