To evaluate the relative performance of clinical readouts including serum C-reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), globulin (GLB) levels, the albumin to GLB ratio (A/G), and the neutrophil to lymphocyte ratio (NLR) when diagnosing periprosthetic joint infection (PJI). Clinical data was collected from 115 individuals diagnosed in our department between January 2017 and December 2020 with either chronic PJI (29 female, 24 male; median age 71.00 years range, 41-94 years) or aseptic loosening (30 female, 32 male; median age 68.50 years range, 34-85 years). Patient demographic data were compared, and the relative sensitivity and specificity of preoperative GLB, ESR, CRP, NLR, and A/G values as predictors of PJI diagnosis were assessed. Median globulin levels in the PJI and aseptic groups were 31.700 g/L (interquartile range IQR, 28.400-35.300) and 26.600 g/L (IQR, 24.375-30.550), respectively (p < 0.001). The median A/G values in the PJI and aseptic groups were 1.150 (IQR, 0.960-1.255) and 1.510 (IQR, 1.265-1.670), respectively (p < 0.001). The median NLR values in the PJI and aseptic groups were 2.510 (IQR, 1.900-3.335) and 1.850 (IQR, 1.425 to 2.362), respectively (p < 0.001). The median ESR values in the PJI and aseptic groups were 53.000 mm/h (IQR, 35.000-76.500) and 16.000 mm/h (IQR, 7.000-33.000), respectively (p < 0.001). Median CRP levels in the PJI and aseptic groups were 24.890 mg/L (IQR, 10.595-54.095) and 2.245 mg/L (IQR, 0.865-8.6075), respectively (p < 0.001). Area under the receiver operating characteristic (ROC) curve (AUC) values for CRP, ESR, GLB, A/G, and NLR were 0.841 (95% confidence interval, 0.761-0.903), 0.850 (0.771-0.910), 0.747 (0.658-0.824), 0.779 (0.692-0.851), and 0.708 (0.616-0.789), respectively. When GLB > 26.6 g/L, A/G < 1.32, and NLR > 2.1 were utilized as threshold values to diagnose PJI, GLB and A/G were found to exhibit superior sensitivity (90.57%, 81.13%) to that observed for CRP (71.70%) and ESR (79.25%), but the specificity of these two metrics (GLB: 51.61%, A/G: 72.58%) was significantly reduced relative to that for CRP (87.10%) or ESR (75.81%). ROC analyses further revealed that NLR did not exhibit significant advantages in sensitivity (73.58%) or specificity (70.97%) relative to CRP or ESR. Globulin levels, NLR values, and A/G values do not outperform ESR or CRP levels when used to diagnose PJI.