Background: Burns that affect ≥20% of the total body surface area (TBSA) trigger a major inflammatory response in addition to capillary leakage and loss of serum proteins including albumin. Persistent hypoalbuminemia is therefore common in major burn patients. The purpose of this study was to determine whether human albumin solutions can benefit major burn patients with persistent hypoalbuminemia. Methods: We conducted a retrospective review of major burn patients with ≥20% of TBSA involved at Taipei Veterans General Hospital between January 2007 and December 2018. Thirty-eight patients were enrolled. Patient demographics, burn characteristics, fluid balance, laboratory results, and outcomes were recorded through chart review. Result: No significant differences were found in the baseline characteristics of patients who received <25 mg/kg/%TBSA/day of human albumin solutions and those who received more than this amount. Renal replacement therapy, duration of mechanical ventilation, length of stay in the burn unit, and in-hospital mortality rate were not statistically different between the two groups. The serum C-reactive protein/albumin ratio was associated with in-hospital mortality (p = 0.036). Conclusion: The administration of large amounts of albumin supplements for the correction of prolonged hypoalbuminemia in major burn patients had no significant benefits on mortality.