This study was designed to validate or refute the reliability of total lymphocyte count (TLC) and other hematological parameters as a substitute for CD4 cell counts. Participants consisted of two groups, including 416 antiretroviral naive (G1) and 328 antiretroviral experienced (G2) patients. CD4+ T cell counts were performed using a Cyflow machine. Hematological parameters were analyzed using a hematology analyzer. The median ± SEM CD4 count (range) of participants in G1 was 199 ± 10.9 (5-1840 cells/µL) and the median ± SEM TLC (range) was 1. 61 ± 0.05 (0.07-6.63 × 10 3 /µL). The corresponding values among G2 were 421 ± 15.8 (13-1801) and 2.13 ± 0.04 (0.06-5.58), respectively. Using a threshold value of 1.2 × 10 3 /µL for TLC alone, the sensitivity of G1 was 88.4% (specificity (SP) 67.4%, the positive predictive value (PPV) 53.5% and negative predictive value (NPV) of 93.2% for CD4 , 200 cells/µL, the sensitivity for G2 was 83.3%, SP 85.3%, PPV 23.8%, and NPV of 93.2%. Using multiple parameters, including TLC , 1.2 × 10 3 /µL, hemoglobin , 10 g/dL, and platelets , 150 × 10 3 /L, the sensitivity increased to 96.0% (SP, 82.7%; PPV, 80%; NPV, 96.7%) among G1, while no change was observed in the G2 cohort. TLC , 1.2 × 10 3 /µL alone is an insensitive predictor of CD4 count of , 200 cells/µL. Incorporating hemoglobin , 10 g/dL, and platelets , 150 × 10 3 /L enhances the ability of TLC , 1.2 × 10 3 /µL to predict CD4 count , 200 cells/µL among the antiretroviral-naïve cohort. We recommend the use of multiple, inexpensively measured hematological parameters in the form of an algorithm for predicting CD4 count level.