Balanced crystalloid solutions induce less hyperchloremia than normal saline, but their role as primary fluid replacement for children undergoing surgery is unestablished. We hypothesized that balanced crystalloids induce less chloride and metabolic derangements than 0.9% saline solutions in children undergoing brain tumor resection. In total, 53 patients (age range, 6 mo to 12 y) were randomized to receive balanced crystalloid (balanced group) or 0.9% saline solution (saline group) during and after (for 24 h) brain tumor resection. Serum electrolyte and arterial blood gas analyses were performed at the beginning of surgery (baseline), after surgery, and at postoperative day 1. The primary trial outcome was the absolute difference in serum chloride concentrations (post-preopΔCl) measured after surgery and at baseline. Secondary outcomes included the post-preopΔ of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a 4-point scale evaluated by the surgeon for assessing brain edema. Saline infusion increased post-preopΔCl (6 3.5; 8.5 mmol/L) compared with balanced crystalloid (0 -1.0; 3.0 mmol/L; P<0.001). Saline use also resulted in increased post-preopΔBE (-4.4 -5.0; -2.3 vs. -0.4 -2.7; 1.3 mmol/L; P<0.001) and hyperchloremic acidosis incidence (6/25 24% vs. 0; P=0.022) compared with balanced crystalloid. Brain relaxation score was comparable between groups. In children undergoing brain tumor resection, saline infusion increased variation in serum chloride compared with balanced crystalloid. These findings support the use of balanced crystalloid solutions in children undergoing brain tumor resection.