Background: Preterm neonates comprise the most heavily transfused group of patients, and about 85% of extremely low birth weight newborns receive a transfusion by the end of their hospital stay. The aim of this study was to assess the possible metabolic effects of RBC transfusion on preterm infants, especially during the first 2 weeks of life, and its relation to blood volume. Materials and Methods: This study was conducted on 40 preterm neonates with gestational age of less than or equal to 34 weeks. They received RBCs transfusion during first 2 weeks of life. Venous blood samples of infants were collected 2 to 4 hours before and 1 hour after the end of transfusion to evaluate hemoglobin (Hb) level, hematocrit, acid-base, electrolytes, and glucose status. Then, infants were classified into two main groups: those who received RBCs volume less than or 20 ml/kg and those who received RBCs volume more than 20 ml/kg. Results: Infants received a mean volume of 20.38 ± 3.2 ml/kg RBCs (range, 10.9 - 26.6 ml/kg) at a median age of 9.8 ± 3.6 days. After transfusion, a significant increase of mean Hb (P<0.001), mean Hct (P<0.001), pH (P<0.001), pO 2 (P<0.05), and a significant decrease of the pCO2 (41.46 ± 8.8torr vs 35.4 ± 9.34 torr; P<0.001) were observed. In addition, there was a significant increase of serum K + (P<0.001), and a significant decrease of Ca +2 (P<0.001). A positive correlation was found between the K + intake and the changes of kalemia (r = 0.99; P = 0.00). Furthermore, we observed an inverse correlation between the patients′ calcium intake and the changes of calcemia (r = -0.35; P = 0.02). On comparing the changes in clinical and biochemical variables between two groups after transfusion, we observed a significant increase in mean Hb and Hct associated with a significant decrease in mean serum Ca +2 (P<0.001) in the group receiving the larger blood volume. Conclusion: RBC transfusion was effective in improving anemia, oxygenation, increasing pH, and decreasing CO 2 and Ca +2 . However, from a more clinically relevant point of view, we demonstrated the development of hyperkalemia, especially in infants with a previously borderline hyperkalemia.