Male partner involvement (MPI) during the prenatal and postnatal periods has been proven to have a beneficial effect on infant development. Infants born to HIV seropositive mothers with lacking or no prenatal and postnatal male partner support may be at a higher risk for adverse developmental outcomes. This study examined the effect of MPI on cognitive, communicative, fine, and gross motor development in 160 infants born to HIV seropositive mothers attending Prevention of Mother-to-Child Transmission of HIV (PMTCT) services in rural South Africa. Results of the bivariate logistic regression showed that both prenatal (OR 1.13; 95% CI 1.01, 1.26; p < 0.05) and postnatal MPI (at 12 months) (1.19; 1.07, 1.31; p < 0.005) were associated with risk for delayed gross motor development in HIV exposed infants. Decreased postnatal MPI (0.85; 0.75, 0.98; p < 0.05) was significantly associated with risk for delayed cognitive development. Not living together with a male partner (2.01; 1.06, 3.80; p < 0.05) was significantly associated with risk for delayed cognitive development. In the multivariate logistic regression analysis, decreased postnatal MPI (0.85; 0.75, 0.98; p < 0.05) was significantly associated with risk for delayed cognitive development. On the other hand, postnatal MPI (1.30; 1.12, 1.50; p < 0.005) was associated with risk for delayed gross motor development among HIV exposed infants. Increased MPI can have beneficial effects on infant's cognitive development. Interventions in PMTCT programs should promote increased prenatal and postnatal MPI to improve cognitive development in HIV exposed infants.