Monitoring and evaluation (M&E) systems are an essential element of functioning and accountable global health programmes. In post-conflict settings, the role of M&E systems is also critical to ensure that health services are being delivered to those populations and regions most in need. Given the inherent challenges of health service delivery in such environments, a range of both diplomatic and operational adaptations to M&E procedures are necessary. Using the '12 components' of a functioning M&E system as a conceptual and analytical framework, we observed and reviewed the key challenges to M&E systems in South Sudan as part of a broader review of United Nations Development Programme (UNDP) activities supported by the Global Fund to Fight AIDS, Tuberculosis and Malaria. Based on additional interview-based reviews and analyses of M&E activities, a list of adaptations to standardized M&E procedures in response to post-conflict environmental challenges was developed. The study concludes that development and implementation of M&E systems in post-conflict environments requires extensive adaptations to conventional procedures. Flexible and adaptable as well as 'diplomatically sensitized' M&E systems are considered to be essential to the successful completion of M&E-related activities, and may also contribute to broader international relations, 'nation-building', and peace-keeping goals.