The maternal factors that contribute to high mortality rates among infants born to women with human immunodeficiency virus (HIV) are unclear. We followed 474 HIV-infected mothers and their infants in Malawi from pregnancy through the infants' 12th month of life. Of the 474 HIV-infected pregnant women, 300 (63.3%) were deficient in vitamin A (serum level of vitamin A, <1.05 micromol/L). Mean serum vitamin A levels among mothers whose infants died were 0.78 +/- 0.03 micromol/L compared with 1.02 +/- 0.02 micromol/L among mothers whose infants had survived for the first 12 months of life (P <.0001). The overall infant mortality rate was 28.7%. We divided HIV-positive mothers into six groups according to serum vitamin A levels (micromol/L) as follows: group 1, <0.35; group 2, between 0.35 and 0.70; group 3, between 0.70 and 1.05; group 4, between 1.05 and 1.40; group 5, between 1.40 and 1.75; and group 6, >1.75. Infant mortality rates for each group were 93.3%, 41.6%, 23.4%, 18.5%, 17.7%, and 14.2%, respectively (P < .0001). Maternal vitamin A deficiency during HIV infection may contribute to increased infant mortality.