Among 453 untreated HIV-infected Zimbabwean infants, 6-week viral load was the only infant factor that independently predicted mortality. Infants with viral load ≥ 1.59 million copies/mL (cohort median) had 3-fold increased mortality through 6 months (hazard ratio 3.07 [95% confidence interval: 2.16, 4.38]; P < 0.001) and 2-fold increased mortality through 12 months (hazard ratio 2.03 [95% confidence interval: 1.41, 2.91]; P < 0.001], compared with infants with viral load below the median.