Recent UNICEF report on the health indicators of India mirror poor maternal and child health conditions, along with practices of early marriage and childbirth during adolescence. At the same time the southern state of Kerala stand out as a beacon of hope. Most of the maternal and child health related indicators of Kerala are still comparable to many developed countries, even though the state's per capita income is low in comparison. The purpose of this paper is to examine the determinants of Infant and child mortality in South India with a comparison to Kerala by using National Family and Health Survey round 3 (NFHS 3) data of 2005-06.Econometrics models are used to assess the determinants. In the analysis all the determinants of infant and child mortality are considered for all the four south Indian states. The mortality of infant and child is found to depend on environmental, biological, socio- economic and behavioural factors. An interesting finding is, the employment status of women is proved to be a significant determinant of child mortality. Children of employed mothers are more vulnerable to mortality than non employed mothers. The educational status of women also showed a significant impact on the survival of their infants and children. The biological and behavioral factors also proved as significant determinant of infant and child mortality in South India.