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Objects: To compare surgical inflammatory response (SIR) after radical cystectomy (RC) in a porcine model using minimal invasive techniques. Additionally we aimed to investigate the potential immunosuppressive ability of preoperative CO 2 -pneumoperitoneum (CO 2 P)., Materials and Methods: Forty female landrace pigs were randomized to five groups: Three intervention groups all having a cystectomy and an ileal conduit either done by robot-assisted laparoscopic technique with intracorporeal urinary diversion (RALC) or an open mini-laparotomy with or without prior CO 2 P (OMC ± CO 2 P). Two control sham groups with or without prior CO 2 P (S ± CO 2 P). Serum samples were obtained preoperatively, immediately postoperative, 24, 48 and 72 hours postoperatively, and the inflammatory mediators CRP, Haptoglobin, Ceruloplasmin, Albumin, Cortisol, IL-4, IL-6, IL-12 and IFN-α were measured., Results: Operative time was significantly longer in RALC compared to open groups (OMC ± CO 2 P) (p's < .0001). CRP and Haptoglobin levels were significantly higher for surgical intervention groups (SIG) compared to controls 24, 48 and 72 hours postoperatively (p's < .001). At 48 hours, CRP was higher for RALC vs OMC + CO 2 P (p = .029). At 72 hours, Haptoglobin was higher for RALC vs open groups (p's < .024). Ceruloplasmin, cortisol, albumin, IL-4, IL-6, IL-12 and IFN-α, revealed no significant differences between SIG., Conclusions: No major differences were found between RALC and OMC regarding the degree of tissue trauma quantified by inflammatory markers. Thirty minutes of CO 2- insufflation preoperative appears to have a transient immunosuppressive effect of the innate postoperative SIR, whereas prolonged CO 2 P apparently diminishes this effect.