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Purpose: To determine whether severe hypoalbuminemia (<25 mg/L) has a significant effect on serum levels of vancomycin and whether it can effect vancomycin dosage regimen and the loading dose administration. Material and Methods: Prospective, cohort, and a single-center study included 61 patients whose vancomycin serum levels were measured in steady state. Vancomycin trough levels (Cmin) that were in the range 15 to 20 μg/mL were considered therapeutic and trough levels higher than 15 μg/mL were considered potentially nephrotoxic. Results: In the group of patients with severe hypoalbuminemia, Cmin was significantly higher compared to the those with nonsevere hypoalbuminemia (>25 mg/L; 23.04 [19.14] vs 13.28 [11.28], P = .01). In the group of patients who received the vancomycin loading dose of 2 g, Cmin was significantly higher in patients with severe hypoalbuminemia compared to the patients with nonsevere hypoalbuminemia (34.52 [25.93] vs 15.37 [10.48], P = .04). Conclusion: In critically ill septic patients with severe hypoalbuminemia, there is a high probability that the loading dose of vancomycin is not necessary since it is associated with potentially toxic vancomycin Cmin, while in the patients with nonsevere hypoalbuminemia the loading dose may be necessary to achieving therapeutic Cmin. [ABSTRACT FROM AUTHOR]