BACKGROUND : In South Africa, 30.9% of children under five years with Severe Acute Malnutrition (SAM) died in 2018. We aimed to identify factors associated with mortality among children under five years hospitalized with SAM in Limpopo province, South Africa. METHODS : We conducted a cross-sectional study including children under five years admitted with SAM from 2014 to 2018 in public hospitals of Limpopo province. We extracted socio-demographic and clinical data from hospital records. We used logistic regression to identify factors associated with mortality. FINDINGS : We included 956 children, 50.2% (480/956) male and 49.8% (476/956) female. The median age was 13 months (inter quartile range: 9–19 months). The overall SAM mortality over the study period was 25.9% (248/956). The most common complications were diarrhea, 63.8% (610/956), and lower respiratory tract infections (LRTIs), 42.4% (405/956). Factors associated with mortality included herbal medication use (adjusted Odds Ratio (aOR): 2.2, 95% Confidence Interval (CI): 1.4–3.5, p = 0.001), poor appetite (aOR: 2.7, 95% CI: 1.4–5.2, p = 0.003), Mid-upper circumference (MUAC) <11.5 cm (aOR: 3.0, 95% CI: 1.9–4.7, p<0.001), lower respiratory tract infections (LRTIs) (aOR: 1.6, 95% CI: 1.2–2.0, p<0.001), anemia (aOR: 2.5, 95% CI: 1.1–5.3, p = 0.021), hypoglycemia (aOR: 12.4, 95% CI: 7.1–21.8, p<0.001) and human immunodeficiency virus (HIV) infection (aOR: 2.3, 95% CI: 1.6–3.3, p<0.001). INTERPRETATION : Herbal medication use, poor appetite, LRTIs, anemia, hypoglycemia, and HIV infection were associated with mortality among children with SAM. These factors should guide management of children with SAM.