Background: The plasma glutamine levels are known to decrease after major surgery, which is related to a negative clinical outcome. However, the influence of surgical stress on the decrease in the plasma glutamine concentration is unclear. The aim of this study was to evaluate the change in glutamine in relation to the types of gastrectomy and approaches as well as the amount of surgical stress evaluated by serum interleukin-6(IL-6) as an objective indicator. Methods: This was a prospective observational study. The eligibility criteria were (1) gastric adenocarcinoma of the stomach confirmed by pathology and (2) patients scheduled to receive gastrectomy with lymphadenectomy for gastric cancer. Blood samples were taken at 7 AM on the day of surgery and at 12 h after surgery to measure the plasma glutamine and interleukin-6 (IL-6) levels. Results: Between May 2011 and December 2011, 81 consecutive patients were enrolled in this study. The plasma glutamine level was significantly decreased in all patients, regardless of distal or total gastrectomy and laparoscopic or open surgery. No significant differences were observed in the IL-6 level between total and distal gastrectomy patients or between patients treated via a laparoscopic or open approach. Decreases in the plasma glutamine level were positively correlated with the logarithmically transformed-plasma IL-6 (logIL6) (r =0.471, p<0.001) overall. Conclusions: Decreases in the glutamine concentration depended on the amount of surgical stress. When conducting a clinical trial to evaluate glutamine administration, personalized adjustment may be key to avoiding glutamine depletion in response to surgical stress.