Background: ALPPS is a novel 2-staged surgical procedure for liver tumors, which induces an unprecedented degree of liver regeneration. Despite the ALPPS induced accelerated regeneration, the postoperative mortality is relatively high, duo to the frequently occurring postinterventional liver failure. Our goal was to assess the background of this increased vulnerability via examination of mitochondrial biogenesis and function after ALPPS. Methods: Male Wistar rats (n=100) underwent ALPPS or portal vein ligation (PVL). The animals were sacrificed before (0) and 24-48-72-168h after the operations and the regeneration rate was calculated. Mitochondrial respiration and ATP production were determined, as well as peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), Nuclear respiratory factor 1– and 2 (NRF1, NRF2) expression and mitochondrial morphology were assessed. Results: After 48h in the ALPPS group the regeneration ratio was significantly higher, while mitochondrial respiration and ATP production decreased significantly compared to the PVL group. The PGC1α and NRF1 concentration was significantly decreased after 48h in the ALPPS group (p=0,004, p<0,001 vs. PVL, respectively), while the NRF2 concentration showed no significant differences. The ratio of smaller than 0,24μm2 mitochondria elevated significantly in the ALPPS group compared to the PVL group (p=0,023). Conclusion: According to our Results ALPPS causes major failures in mitochondrial biogenesis and function.