Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) have been investigated as disease activity markers for systemic lupus erythematosus (SLE). Hence, we investigated the clinical significance of these parameters in diagnosing infection in patients with SLE. In total, 120 patients with SLE, who were admitted to hospital due to disease flares or infection, were recruited for the study. Of the 120 patients, 60 had a concurrent infection (SLE with infection), while the remaining 60 patients were admitted with a flare without any evidence of infection (SLE with flare). NLR was higher in the patients with SLE with infection, compared to patients with SLE with flare (14.2 +/- 15.4 versus 3.3 +/- 2.2, p < 0.001). Additionally, PLR was higher in the SLE with infection group than in the SLE with flare group (357.7 +/- 350.1 versus 231.7 +/- 152.9, p = 0.012), but not MLR. In the SLE with infection group, C-reactive protein (CRP) levels positively correlated with NLR and PLR. NLR with a cut-off value of 5.70 and an area under the curve (AUC) of 0.872 indicated good sensitivity (75%) and specificity (90%), for the diagnosis of SLE with infection. CRP with a cut-off value of 1.28 mg/dL (AUC 0.942) showed the sensitivity (93.3%) and specificity (91.7%). NLR with a cut-off value of 5.70 and CRP with a cut-off value of 1.28 mg/dL showed the increased specificity (98.3%) than only CRP, but not significant. NLR could be a good additive marker for diagnosing infection in patients with SLE.