Red blood cell distribution width (RDW) is a routine parameter that reflects size variations in erythrocytes. High RDW has been associated with cardiovascular events and inflammatory diseases. However, no studies evaluating the association of RDW with systemic lupus erythematosus (SLE) have been published. We aimed to explore the association of RDW with inflammatory markers in SLE. As SLE is often associated with anaemia, we considered this factor in order to know whether RDW is related with inflammation, anaemia or both in SLE. The study included 105 SLE patients (7 men, 98 women; aged 15-73 years) and 105 controls (9 men, 96 women; aged 18-71 years). Patients were divided according to anaemia status (26 with, 79 without). Biochemical, hematological and inflammatory parameters (C-reactive protein (CRP), fibrinogen and erythrocyte aggregation (EA1)) were analyzed. SLE patients showed increased RDW, CRP and EA1 (p < 0.001), and decreased hemoglobin levels (p < 0.001) when compared with controls. RDW was higher in SLE patients with anaemia (a-SLE) as compared with those without anaemia (na-SLE) (p < 0.01) or controls (p < 0.001). CRP in a-SLE was higher than in controls (p < 0.01) but lower than in na-SLE (p < 0.05). In na-SLE RDW correlated directly with fibrinogen and CRP (p < 0.001), but not in a-SLE. Our results indicate that SLE patients show higher RDW irrespectively of anaemia status, and that RDW is influenced by both anaemia and inflammation, but the influence of anaemia is stronger.