Background Indirect effects of the COVID-19 pandemic on communities in fragile and conflict-affected settings may be severe due to reduced access and use of healthcare, as happened during the 2015 Ebola Virus Disease outbreak. Achieving a balance between short-term emergency response and addressing long-term health needs is particularly challenging in fragile and conflict-affected settings such as South Sudan, given the already significant barriers to accessing healthcare for the population. This study sought to characterise the effect of COVID-19 on healthcare access and South Sudan’s healthcare response. This can inform efforts to mitigate the potential impacts of COVID-19 or other epidemiological threats, and contribute to understanding how these may be balanced for greater health system resilience in fragile contexts. Methods We conducted a mixed methods study in three of South Sudan’s states, combining data from a cross-sectional quantitative household survey with qualitative interviews and Focus Group Discussions. Results Even though some fears related to COVID-19 were reported, we found these did not greatly dissuade people from seeking care and do not yield significant consequences for health system programming in South Sudan. The pillars of the response focused on risk communication and community engagement were effective in reaching communities through different channels. Respondents and participants reported behaviour changes that were in line with public health advice. We also found that the implementation of COVID-19 response activities sometimes created frictions between the national government and international health actors, and that COVID-19 caused a greater reliance on, and increased responsibility for, international donors for health planning. Conclusions Given the fact that global priorities on COVID-19 are greatly shifting, power dynamics between international health agencies and the national government may be useful to consider in further COVID-19 planning, particularly for the vaccine roll-out. South Sudan must now navigate a period of transition where COVID-19 vaccine roll-out continues and other domestic health burdens are re-prioritised.