12131 Background: Older adults with cancer often present with suboptimal muscle quantity and quality prior to treatment due to disease-related catabolic effects combined with the aging process. Muscle catabolism is further exacerbated by cancer treatments leading to worse metabolic health, patient quality of life, and clinical outcomes. Our objective was to examine the impact of sarcopenia and myosteatosis on severe laboratory toxicity and overall mortality in older adults with cancer receiving chemotherapy. Methods: This was a retrospective cohort study of older adults who had undergone chemotherapy at the Princess Margaret Cancer Centre, Toronto, Canada from June 2015 to June 2022. A computed tomography scan after diagnosis but prior to treatment was used to assess skeletal muscle index (SMI) and skeletal muscle density (SMD) for each participant. Sarcopenia was defined as the presence of low muscle strength (grip strength <35.5kg for males and <20kg for females), low SMI, and low physical performance (walking speed <0.8m/s or a total Short Physical Performance Battery score of ≤8) prior to chemotherapy initiation. Myosteatosis was assessed through SMD in Hounsfield Units using previously published cut-offs. Severe laboratory toxicity was defined as occurrence of a grade ≥3 adverse event per the Common Terminology Criteria for Adverse Events (version 4.0). Severe laboratory toxicity and overall mortality were assessed from treatment initiation until treatment termination or loss to follow up. Multivariable logistic regression was used to determine the role of sarcopenia and myosteatosis in predicting occurrence of severe laboratory toxicity. Multivariable Cox regression was used to assess the risk of overall mortality. Results: A total of 115 older adults (mean age: 77.1 y) were included, of whom 63.5% had metastatic disease. Sarcopenia was identified in 27% of the cohort, whereas 80% had myosteatosis. A total of 132 severe laboratory toxicities occurred during the study period in 41 participants (35.7%). Sarcopenia was a significant predictor of severe laboratory toxicity (adjusted odds ratio (aOR)=3.19, 95%CI= 1.19 to 8.52, p= 0.012) after adjusting for sex, body mass index, and hemoglobin. Myosteatosis was significantly associated with overall mortality (adjusted hazard ratio (aHR)= 2.51, 95%CI= 1.12-5.61, p=0.025) after adjusting for albumin, alkaline phosphatase, and treatment intent. Conclusions: Sarcopenia may be used to inform the risk of severe laboratory toxicity in older adults prior to chemotherapy. Pre-treatment myosteatosis defined by low SMD predicts overall mortality in the same cohort. Optimization of skeletal muscle health through targeted exercise and nutritional interventions may improve patient quality of life and clinical outcomes in older adults with cancer receiving chemotherapy.