Background Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with wide variety of clinical presentations. Recently, red blood cell distribution width (RDW) has been used as an inflammatory marker, similar to the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) where systemic inflammation has been linked to increased RDW. Many researches have assessed independently selective different hematological markers that may reflect disease activity. Our study aims to examine a number of hematological parameters that could reflect disease activity and to assess if there is a relationship between different hematological parameter (RDW, neutrophils and lymphocytes) to reflect SLE activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Results The study comprised 60 SLE patients (52 females and 8 males) with a mean age of 34.53 years and mean disease duration was 4.085 years. The RDW values were significantly higher (p < 0.001) when comparing active patients (16.64 ± 4.7) versus inactive patients (13.16 ± 2.67) and controls (12.7 ± 1.13). Otherwise, insignificant differences were reported when comparing inactive SLE patients versus the control group (p = 0.242). There were no significant correlations (p > 0.05) between neutrophil count and lymphocyte count with C3, C4, SLEDAI score, 24 h urinary proteins, platelets count but significant only with hemoglobin level (p = 0.001). Conclusion Increased RDW is connected with active disease status of SLE patients. RDW could be used as a surrogate marker of the inflammation rather than neutrophil and lymphocyte count. It is a simple and easy testing included in CBC thus RDW could be used as a possible indicator to assess disease activity.