Background <p>The immediate perioperative period (IPP) usually is highly stressful and has significant effects on the postoperative recurrence/metastasis of tumors. Effective methods for limiting the impact of the IPP on postoperative recurrence/metastasis of tumors remain scarce. We aimed to determine the effects of dexmedetomidine (DEX) treatment during the IPP on postoperative recurrence/metastasis of tumors and the stress response.</p> Materials and methods <p>The clinical perioperative setting was mimicked via tumor resection and perioperative restraint stress in tumor-bearing mice with or without DEX during the IPP. The stress response was assessed using stress hormone and interleukin (IL)-6 levels in peripheral blood. Tumor cell growth was measured via in vivo bioluminescent imaging, cell viability assay, wound-healing assay, and Western blotting.</p> Results <p>In tumor-bearing mice, DEX during the IPP limited the growth of implanted tumor cells and stress response in a dose-dependent manner. The serum from mice without DEX promoted cultured tumor cell growth, which was alleviated by beta-adrenergic receptor blocker propranolol or IL-6 antibody. Relative to the serum from mice without DEX, the serum from mice with DEX had lower stress hormone and IL-6 levels, as well as weaker effects on tumor growth promotion. Dexmedetomidine supplementation during culture had no significant effects on tumor cells.</p> Conclusions <p>Dexmedetomidine alleviates the pro-tumor activity of perioperative stress in abdominal tumors.</p>