Healthcare-associated infections (HAIs) remain a major contributor to morbidity and mortality in intensive care units (ICUs), particularly in low- and middle-income countries (LMICs), where surveillance data from rural tertiary centres are limited. This study determined the prevalence, risk factors, and mortality impact of HAIs among patients admitted for more than 48 hours to adult and paediatric ICUs at Nelson Mandela Academic Hospital between January 2024 and December 2025. A retrospective cross-sectional design was used, and HAIs were defined using standard ≥48-hour post-admission criteria. Logistic regression analysis identified independent predictors of HAI occurrence. Among 266 patients (median age 6.5 years), the prevalence of HAIs was 28.95%. Ventilator-associated pneumonia was the most frequent infection, followed by central line-associated bloodstream infection and catheter-associated urinary tract infection. Prolonged ICU stay (>8 days) independently predicted HAI (adjusted odds ratio 4.51; p<0.001). HAIs were significantly associated with increased mortality compared with non-HAI patients (46.8% vs. 19.0%; p<0.001), with infants disproportionately affected. These findings demonstrate a substantial HAI burden and associated mortality in this rural ICU setting, underscoring the need for strengthened infection prevention bundles and early risk-stratification strategies in resource-limited environments.