Background:Choosing an appropriate fluid therapy for patients during the surgery to have glucose and electrolyte balance and the lack of studies addressing children in this regard, the present study aimed at investigating the effect of different fluid therapy methods on blood sugar (BS), blood gases, and blood electrolytes in cancer children undergoing major surgery. Materials and Methods: The current clinical trial was conducted on 58 children aged 1 year to 5years that were candidates for surgery. These patients were randomly divided into two groups undergoing intraoperative fluid therapy with Ringer Lactate and 5%dextrose in 0.9% saline. The values of hemodynamic parameters, BS, serum electrolytes (sodium, potassium, and chloride), and blood gases (pH, HCO3, and BE) were evaluated and compared among the three groups. Results: The level of BS at the end of the surgery in Ringer’s group was lower with mean 142.1±27.04mg/dl was significantly lower than its level in dextrose 5% in 0.9%saline: 189.20 ± 34.23; P value <<0.001)and after 24 hrs with mean167.45±36.73 in Ringer Lactate group in comparison to D5W with mean value 264.38±39.87;P value<0.001.The level of sodium In comparison to mean value ofNa level at end of surgery, there was asignificant increase in Ringer Lactate group than D5W (P value = 0.032) and after 24h, there was a significant decrease in Ringer Lactate than D5W (P value = 0.007).The pH level In comparison to mean value of pH at end of surgery, there was a significant decrease in Ringer Lactate than D5W (P value <0.001).On the contrary, HCO3, and lactate levels at the end of the surgery had no significant differences between the two groups . The amount of urine output at all follow-up times revealed a significant difference between Ringer’s group and the other two groups (P value < 0.001).Heart rate and MAP measurements were insignificantly different between both groups. Conclusion: Our finding concluded that ringer lactate solutions could significantly maintain the acid-base balance and glucose level and electrolytes balance in the perioperative period in children undergoing major surgeries compared to traditional 5% glucose in 0.9%saline.