Background: The purpose of this study was to examine the association between baseline skeletal muscle measurements, acute toxicity (immune effector cell–associated neurotoxicity syndrome [ICANS], cytokine release syndrome), and treatment efficacy in patients undergoing CAR T-cell therapy for B-lineage lymphoma. Patients and Methods: Skeletal muscle measurements were obtained from automated CT measurements in 226 consecutive patients who received CAR T-cell therapy between 2015 and 2021. The Kaplan-Meier method was used to examine progression-free survival (PFS) and overall survival (OS) at 1-year. Multivariable regression was used to calculate the hazard ratio (HR) with 95% confidence intervals, adjusted for covariates. Results: The median age of the cohort was 63.1 years (range, 18.5–82.4 years), and most patients were male (66%) and had primary refractory disease (58%). Patients with abnormally low skeletal muscle at baseline were at greater risk of ICANS (HR, 1.74; 95% CI, 1.05–2.87) and had longer length of hospitalization (mean 27.7 vs 22.9 days; PPConclusions: This information can be used for risk stratification prior to CAR T-cell therapy or to implement prehabilitation and nutritional optimization before lymphodepletion as well as thereafter. These efforts will be complementary to ongoing efforts toward sustained efficacy after CAR T-cell therapy.