Background: Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is the standard of care for muscle invasive bladder cancer and has a high rate of complications. Malnutrition is common among RC patients and is an established risk factor for peri-operative complications. The association of NAC and nutritional status and its effect on post-operative complications is not fully understood. We hypothesize that NAC hinders nutritional status and thus increases complication rates after RC. Methods: We retrospectively examined the records of NAC/RC patients. We included demographic, clinical and pathologic data and type and cycle number of NAC. Nutritional status was assessed with the smooth muscle area (SMA) of the psoas muscle at the level of L4 vertebrae measured on cross-sectional imaging. Patients with missing imaging data were excluded. SMA was measured pre and post NAC. The difference between the measurements was used as a predictor variable (delta_SMA). The outcomes assessed were ileus, infection, rehospitalization and a composite outcome of any complication. Results: The study included 50 patients, from 3 high volume centers in Israel. Median delta_SMA was -197 (-366, -88) mm². Demographic, clinical and pathologic parameters were similar in patients with and without complications. delta_SMA was an independent predictor of ileus (OR = 0.98, p=0.003), peri-operative infection (OR = 0.98, p=0.0015) and any complications (OR = 0.98, p = 0.011) on univariable analysis. Delta_SMA remained an independent predictor of ilieus (OR 0.97, p=0.014), peri-operative infections (OR 0.95, p=0.023) and any complications (OR 0.98, p=0.01) on multivariable regression analysis. Delta_SMA was not a significant predictor of rehospitalization. Conclusions: In patients undergoing RC, NAC causes a measurable nutritional insult. The change in SMA predicts significant peri-operative complications. Future studies should examine the role of nutritional intervention during NAC in the framework of a clinical trial.