Low skeletal muscle radiodensity (SMD) is related to higher mortality in several cancers, but the association with colorectal cancer (CRC) prognosis is unclear. This observational study included 3262 men and women from the Kaiser Permanente Northern California population diagnosed between 2006 and 2011 with AJCC stages I to III CRC. The authors evaluated hazard ratios (HRs) of low SMD for all-cause and CRC-specific mortality, assessed by computed tomography using optimal stratification, compared with patients with normal SMD. They also evaluated the cross-classification of categories of low versus normal SMD and muscle mass (MM) with outcomes. The median follow-up was 6.9 years. Optimal stratification cutpoints for SMD were 32.5 in women and 35.5 in men. In multivariate-adjusted analyses, among patients with CRC, those with low SMD demonstrated higher overall (HR, 1.61; 95% confidence interval [95% CI], 1.36-1.90) and CRC-specific (HR, 1.74; 95% CI, 1.38-2.21) mortality when compared with those with normal SMD levels. Patients with low SMD and low MM (ie, sarcopenia) were found to have the highest overall (HR, 2.02; 95% CI, 1.65-2.47) and CRC-specific (HR, 2.54; 95% CI, 1.91-3.37) mortality rates. In patients with CRC, those with low SMD were found to have elevated risks of disease-specific and overall mortality, independent of MM or adiposity. Clinical practice should incorporate body composition measures into the evaluation of the health status of patients with CRC. Cancer 2018;124:3008-15. © 2018 American Cancer Society.