In a cohort study of mothers and their infants, information was collected from women attending the antenatal services of two hospitals in a rural area of Malawi and 561 of their babies were enrolled in a follow-up study. There were 128 with a low birthweight (LBW, <2500 g), 138 with fetal anaemia (FA, cord haemoglobin <12.5 g/dl), 42 with both and 228 with a normal birthweight and no FA. Infants were seen monthly for 1 year. Risk factors for post-neonatal infant mortality (PNIM) were calculated using Cox regression analysis adjusting for LBW and FA. PNIM was 9.3%. Respiratory infections and diarrhoeal disease were the principal attributable causes of death. PNIM increased with LBW (RR 3.08, 95% CI 1.51-6.23) but not significantly so with FA (RR 1.60, 95% CI 0.78-3.27). An additional effect on PNIM was observed with maternal HIV (RR 3.44, 95% CI 1.63-7.26) and malaria at the first antenatal visit (RR 2.26, 95% CI 1.09-4.73). Illiteracy was not associated with mortality. Placental malaria in HIV-seronegative mothers was significantly associated with increased PNIM. Improving birthweight through effective antimalarial control in pregnancy will lead to a reduction in PNIM. Reduction of HIV prevalence and prevention of mother-to-child transmission of HIV must be a main target for government health policy.