Aim: There are currently debates about why South Africa integrates global health into its foreign policy agendas. This study aimed at exploring motivation and interests’ South African policy actors pursue to advance global health and the processes that lead to such integration.Methods: The study utilized a mixed-method design from a sample of state policy actors at the National Department of Health of South Africa. Participants were selected purposively and had experience of more than three years participating in various international health activities. All participants completed semi-structured questionnaires. Quantitative data was analysed to determine frequencies and transcribed text was analyzed using qualitative content analysis.  Results: A total of 40 people were invited, of whom 35 agreed to participate. Of the respondents, 89.7% (n=32) strongly argued that health should facilitate ‘free movement of people, goods and services’. Majority (79.0%, n= 29) agreed that ‘development and equality’ are the main elements of foreign policy. Of the respondents, majority 77.1% (n=27) agreed that ‘moral and human rights’ are the main elements of foreign policy. Furthermore, 82.8% (n=29) agreed that the country should advance ‘Africa regionalism and south-south cooperation’ and 85.7% (n=30) strongly argued for a ‘whole-government approach’ in addressing global health challenges. ‘HIV/AIDS’ and ‘access to medicines agenda’ were the main policy issues advanced. The main domestic factors shaping South Africa’s involvement in global health were its ‘political leadership’ and ‘capacity of negotiators’.Conclusion: It is evident that within South Africa, state policy actors are largely concerned with promoting global health interest as a normative value and a goal of foreign policy, namely, human dignity and development cooperation. Furthermore, South Africa drives its global health through building coalition with other state and non-state actors such as civil society. HIV/AIDS, as a policy issue, presents a potential entry point for engagement in global health diplomacy.