A retrospective study was conducted, and 576 human immunodeficiency virus–infected children with total lymphocyte count (TLC) and CD4 count were recruited from China. Spearman rank order correlation and receiver-operating characteristic were used. An overall positive correlation was noted between TLC and CD4 count (prehighly active antiretroviral therapy [pre-HAART], r = 0.789, 6 months of HAART, r = 0.642, 12 months of HAART, r = 0.691, P = 0.001). TLC ≤ 2600 cells/mm3 predicted a CD4 count of ≤350 cells/mm3 with 82.9% sensitivity, 79.6% specificity pre-HAART. Meanwhile, the optimum prediction for CD4 count of ≤350 cells/mm3 was a TLC of ≤2400 cells/mm3 at 6 months (73.6% sensitivity and 74.1% specificity) and 12 months (81.7% sensitivity and 76.5% specificity) of HAART. TLC can be used as a surrogate marker for predicting CD4 count of human immunodeficiency virus–infected children before and during HAART in resource-limited countries.