Abstract Background The under-five mortality rates of children in South Africa (SA) remain high despite successful HIV prevention and treatment programs. The in-hospital mortality of children with severe acute malnutrition remains a key obstacle. This study identifies and describes changes in the mortality of under-five children with severe acute malnutrition (SAM) following the implementation of HIV and malnutrition prevention and treatment programmes. Methods This was a retrospective review of in-hospital mortality records and databases. The study was based at a large referral hospital in KwaZulu-Natal (KZN), where HIV and malnutrition rates are high, and SAM children are managed with standard WHO guidelines. Records of children under five years old who died from 2009 to 2018 were analysed. Results Of the 698 under-five children who died in this period, 285 (40, 8% of all under-5 deaths) were classified as having SAM. The number of HIV-infected SAM deaths dropped significantly, especially those below six months of age, mirroring the expansion of HIV treatment and prevention programmes. Despite this and a significant drop in the proportion of SAM admissions identified, there was no change in SAM case fatality rates over the ten years. Septicaemia remained the most common cause of death in children with SAM. Conclusions Despite significant decreases in HIV-related malnutrition deaths over ten years, the lack of change in SAM case fatality rates is a concern at this referral hospital. Standardised WHO inpatient management protocols, may require review, especially where underlying medical conditions may contribute to SAM deaths in HIV-negative children.