Background and Aims It has been proven that enhanced recovery after surgery (ERAS) offers advantages for patients undergoing surgery. However, the effects of ERAS on cellular immune function and stress response at the molecular level in patients undergoing radical gastrectomy are still rarely reported. Therefore, this study was conducted to investigated the effects of ERAS concept and protocol on tumor cell immunity, inflammatory factors and stress hormones in patients undergoing laparoscopic radical gastrectomy.Methods From January 2018 to December 2020, 90 patients with gastric cancer undergoing laparoscopic radical gastrectomy were selected and divided into ERAS group (43 cases) and control group (47 cases). The patients in ERAS group received ERAS perioperative management, while those in control group received the traditional perioperative management. The general clinical data (sex, age, BMI, ASA grade, TNM stage, and tumor size), surgery related variables (surgical procedure, anastomosis method, operative time, intraoperative blood loss, and lymph node dissection), and postoperative variables (time to postoperative ambulation, time to postoperative anal gas passage, length of hospitalization, and postoperative complications) were compared between the two groups. The percentages of positive immunoregulatory cells (CD3⁺CD4⁺T cells, CD3⁺CD8⁺T cells and CD16⁺CD56⁺NK cells), negative immunoregulatory cells [granulocytic myeloid-derived suppressor cells (G-MDSC), monocytic myeloid-derived suppressor cells (M-MDSC) and regulatory T cells (Treg)] and regulatory B cells (Breg) in the peripheral blood at 1 and 7 d after operation, as well as the levels of stress response indexes that included cortisol (COR), adrenocorticotropic hormone (ACTH), epinephrine (EPI) and C-reactive protein (CRP) and the inflammatory factors that included the interleukin-6 (IL-6) before and 24 h after operation were compared between the two groups.Results There was no significant difference in terms of sex, age, BMI, ASA grade, TNM stage, tumor size, surgical procedure, anastomosis method, operative time, intraoperative blood loss and number of lymph node dissection between ERAS group and control group (all P>0.05). Both times to postoperative ambulation and first postoperative anal gas passage in ERAS group were significantly earlier than those in control group (25.01 h vs. 37.01 h, P=0.000; 74.51 h vs. 135.31 h, P=0.000), the length of hospitalization in ERAS group was significantly shorter than that in control group (7.01 d vs. 9.81 d, P=0.000), and the overall incidence rate of postoperative complications in ERAS group was significantly lower than that in control group (9.3% vs. 19.1%, P=0.027). At 1 and 7 d after operation, the percentages of CD3⁺CD4⁺T cells, CD3⁺CD8⁺T cells and CD16⁺CD56⁺NK cells in ERAS group were higher than those in control group, while the percentages of G-MDSC, M-MDSC and Treg cells as well as Breg cells in ERAS group were lower than those in control group (all P<0.05). There was no significant difference in concentrations of COR, ACTH and EPI as well as CRP and IL-6 between ERAS group and control group before operation (all P>0.05), but above parameters were significantly lower in ERAS group than those in control group at 24 h after operation (all P<0.05).Conclusions Using ERAS concept during perioperative period of laparoscopic radical gastrectomy can decrease the interference of surgical trauma on cellular immunity, enhance the positive immune regulation, inhibit negative immune regulation, and reduce the inflammatory and stress responses.