Central line-associated bloodstream infection (CLABSI) and catheter-related bloodstream infection (CLABSI with a positive catheter tip culture, CRBSI) are preventable causes of morbidity and mortality for severe adult burns patients. Routine central line changes as a CLABSI prevention strategy in burns patients is controversial due to the paucity of evidence to guide the appropriate timing of line changes. This study aimed to address this evidence gap by investigating risk factors associated with central line sepsis, including the duration of central line insertion, in a population of severe adult burns patients (burns involving ≥20% total body surface area (TBSA)) admitted to the Royal Brisbane and Women’s Hospital Intensive Care Unit over five years (2015–2019 inclusive). On multivariate analysis, central line duration and burn TBSA were identified as independent risk factors for CLABSI, with central line duration the most significant predictor (p = 0.0008; OR 1.177, 95% CI 1.072–1.299). No risk factor independently predicted CRBSI. CLABSI detection occurred a median of 8.5 days (IQR 6.0–11.0) post central line insertion. These findings suggest further research to assess the efficacy of routine line changes prior to the at-risk period of 6–11 days post central line insertion in reducing CLABSI in severe adult burns patients may be beneficial.