The aim of this study was to analyse the dynamics of tissue damage and inflammatory response markers perioperatively and whether these differ between women operated with robotic and abdominal hysterectomy in treating early-stage endometrial cancer. At a Swedish university hospital fifty women with early-stage low-risk endometrial cancer were allocated to robotic or abdominal hysterectomy in a randomiszed controlled trial. Blood samples reflecting inflammatory responses (high sensitivity CRP, white blood cells (WBC), thrombocytes, IL-6, cortisol) and tissue damage (creatine kinase (CK), high-mobility group box 1 protein (HMGB1)) were collected one week preoperatively, just before surgery, postoperatively at two, 24 and 48 hours, and one and six weeks postoperatively. High sensitivity CRP (p = 0.03), WBC (p < 0.01), IL-6 (p = 0.03) and CK (p = 0.03) were significantly lower in the robotic group, but fast transitory. Cortisol returned to baseline two hours after robotic hysterectomy but remained elevated in the abdominal group comparable to the preoperative high levels for both groups just before surgery (p < 0.0001). Thrombocytes and HMGB1 were not affected by the mode of surgery. Postoperative inflammatory response and tissue damage were lower after robotic hysterectomy compared to abdominal hysterectomy. A significant remaining cortisol elevation two hours after surgery may reflect a higher stress response in the abdominal group.