Frailty has been implicated as a negative predictor of Liver Transplant (LT) outcomes. However, an understanding of changes in patient muscle mass peri-LT, and their effect in high-acuity patients remains lacking.We examined the impact of perioperative muscle mass changes (ΔSMI) on high-acuity (MELD ≥35) LT recipients. Skeletal muscle index (SMI) was calculated using CT imaging. Patients were divided into two groups, based on severity of peri-operative SMI decrease. LT recipients with chronic end-stage liver disease, MELD ≥35, and abdominal CT ≤30 days prior, and 30-90 days post LT were included. [1011 adult LT recipients reviewed, 2012-2018]. Of 1011 patients reviewed, 88 met inclusion criteria (median MELD 41.1). The median ΔSMI was -5.0 (-29.4 - +21.1 cm2/m2) (fig A). Patients were classified into two groups: ΔSMI<-5.0 (median ΔSMI: -0.4, n=44) and ΔSMI>-5.0 (median ΔSMI: -9.2, n=44). Recipients with ΔSMI<-5.0 had higher pre-LT SMI (35.4 versus 31.2 cm2/m2, P <0.001) and lower post-LT SMI (26.0 versus 30.8 cm2/m2, P <0.001). The ΔSMI<-5.0 group had higher early allograft dysfunction (40.9 versus 20.5%, P=0.037), and inferior patient and graft survival (P=0.015, 0.017, respectively). Multivariate analysis identified ΔSMI<-5.0 (HR: 2.938, P=0.048), long cold-ischemia time (≥9h, HR: 7.332, P=0.008), HCV (HR: 5.614, p=0.001), and tracheostomy after LT (HR:9.218, P <0.001) as negative prognostic factors for patient survival . Progressive perioperative sarcopenic deterioration was associated with inferior patient and graft survival in high acuity LT. These findings may guide pre and post-operative patient care and rehabilitation efforts in this challenging patient population.