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Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have recently been investigated as two new inflammatory markers used in the assessment of systemic inflammation in many diseases. The purpose of the study was to investigate their relation with disease activity in newly diagnosed SLE patients.The study population consisted of 116 SLE patients who did not receive any treatment and 136 healthy controls. We divided the patients into two groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K) system. Group 1 included patients with a score of 9 and lower (patients with mild disease activity), and Group 2 included patients with a score of > 9 (patients with severe disease activity). Correlations between NLR, PLR and disease activity were analyzed.The NLR and PLR of SLE patients were significantly higher compared to those of the controls (both P < 0.001). There was a statistically significant difference in NLR and PLR between Group 1 and Group 2 (both P < 0.05). SLEDAI scores positively correlated with NLR (r = 0.312, P < 0.001) and PLR (r = 0.298, P < 0.001). Furthermore, SLE patients with nephritis had higher NLR levels than those without nephritis (P = 0.027). Based on the ROC curve, the best NLR cut-off value to predict SLE patients with severe disease activity was 2.26, with 75% sensitivity and 50% specificity, whereas the best PLR cut-off value was 203.85, with 42.3% sensitivity and 83.9% specificity.NLR and PLR were two useful inflammatory markers for assessment of disease activity in patients with SLE.NLR and PLR levels were increased in SLE patients.NLR and PLR were significantly positive associated with SLEDAI-2K scores.NLR was correlated with hs-CRP, C3 and C4NLR was significantly increased in SLE patients with nephritis.