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Although different clinical and experimental parameters have been used to estimate disease activity in systemic lupus erythematosus (SLE) patients, the relationship between red blood cell distribution width-to-platelet ratio (RPR) and disease activity in SLE has not been previously illuminated. Therefore, the aim of this study was to investigate the association between RPR levels and disease activity in SLE.This study enrolled 105 SLE patients and 105 healthy subjects. We divided the patients into 2 groups using the SLE Disease Activity Index (SLEDAI) 2000. Group 1 included patients with SLEDAI score ≤9 (mild disease activity group) and group 2 with SLEDAI >9 (severe disease activity group). Correlations between RPR and disease activity were then analyzed. A subgroup follow-up analysis of 93 patients was conducted to explore the effect of SLE-related glucocorticoid therapy.The PLR and RPR values of SLE patients were significantly higher compared with the controls (both P < .001), whereas mean platelet volume was decreased (P < .05). The RPR level was found to be positively correlated with SLEDAI (r = 0.368, P < .001) and erythrocyte sedimentation rate (r = 0.313, P = .027). According to the receiver-operating characteristic (ROC) curve, the optimal cut-off value for predicting SLE using RPR was 0.073, and the area under ROC curve was 0.817. RPR level was correlated with clinical disease activity in SLE, and its value was normalized after treatment.RPR may be a useful measurement for the assessment of disease activity in SLE patients.