Introduction: This study aimed to evaluate the incidence of hypernatremia and hypokalemia and predisposing factors during IV fosfomycin treatment. Materials and Methods: In this retrospective and cross-sectional study conducted at a university hospital, patients who received intravenous fosfomycin therapy between September 2021 and August 2022 were included. Demographic characteristics, comorbidities, and clinical and laboratory data of the included patients during their stay in the intensive care unit were extracted from the hospital information management system. The analyses were conducted using the SPSS 20.0 software. Results: The mean age of the 62 patients included in the study, 24 of whom were women, was 58.8 ± 19.5 years. Following IV fosfomycin treatment, it was observed that 26 (41.9%) patients developed hypernatremia, with an average onset time of 4.81 ± 1.7 days. There was a statistically significant difference between patients with and without hypernatremia in terms of APACHE II scores (t= 2.246; p< 0.05), the presence of enteral nutrition (p= 0.020), and albumin replacement (p= 0.007). In all patients who developed hypernatremia, fosfomycin was diluted with 0.9% NaCl solution. After IV fosfomycin treatment, 21 (33.9%) patients developed hypokalemia, with an average onset time of 3.90 ± 1.14 days. There was a statistically significant difference between the patients with and without hypokalemia in terms of the presence of albumin replacement (p= 0.004). Conclusion: The incidence of hypernatremia observed in this study was higher than the rates reported in previous studies. The APACHE II score, enteral nutrition, and albumin replacement appear to be significant predisposing factors in hypernatremic patients. Fosfomycin is recognized for its stability not only in 0.9% NaCl solution but also in 5% glucose solution. In patients susceptible to hypernatremia, the use of a 5% glucose solution to dilute fosfomycin could be considered as a preferable option, unless contraindicated.