Objective To explore the feasibility of health systems strengthening from the perspective of international healthcare implementers and donors in South Sudan. Design A qualitative interview study, with thematic analysis using the WHO health system building blocks framework. Setting South Sudan. Participants 17 health system practitioners, working for international agencies in South Sudan, were purposively sampled for their knowledge and experiences of health systems strengthening, services delivery, health policy and politics in South Sudan. Results Participants universally reported the health workforce as insufficient and of low capacity and service delivery as poor, while access to medicines was restricted by governmental lack of commitment in undertaking procurement and supply. However, progress was clear in improved county health department governance, health management information system functionality, increased health worker salary harmonisation and strengthened financial management. Conclusions Resurgent conflict and political tensions have negatively impacted all health system components and maintaining or continuing health system strengthening has become extremely challenging. A coordinated approach to balancing humanitarian need particularly in conflict-affected areas, with longer term development is required so as not to lose improvements gained.