The optimal ventilation strategy during cardiopulmonary resuscitation (CPR) has eluded scientists for years. This porcine study aims to validate the hypothesis that ultra-low tidal volume ventilation (tidal volume 2–3 mL kg−1; ULTVV) minimizes renal and hepatic end-organ damage when compared to standard intermittent positive pressure ventilation (tidal volume 8–10 mL kg−1; IPPV) during CPR. After induced ventricular fibrillation, the animals were ventilated using an established CPR protocol. Upon return of spontaneous circulation (ROSC), the follow-up was 20 h. After sacrifice, kidney and liver samples were harvested and analyzed histopathologically using an Endothelial, Glomerular, Tubular, and Interstitial (EGTI) scoring system for the kidney and a newly developed scoring system for the liver. Of 69 animals, 5 in the IPPV group and 6 in the ULTVV group achieved sustained ROSC and were enlisted, while 4 served as the sham group. Creatinine clearance was significantly lower in the IPPV-group than in the sham group (p < 0.001). The total EGTI score was significantly higher for ULTVV than for the sham group (p = 0.038). Aminotransferase levels and liver score showed no significant difference between the intervention groups. ULTVV may be advantageous when compared to standard ventilation during CPR in the short-term ROSC follow-up period.