Background: Insulin growth factor-1 (IGF1) and inflammatory biomarkers such as interleukin-6 (IL6) play a role in early carcinogenesis, predict prognosis and response to some therapies in colorectal cancer (CRC), and are altered in patients with sarcopenia. This study examines the association of IGF-1 and IL-6 with sarcopenia in patients with CRC. Methods: Fasting blood samples were collected at diagnosis of non-metastatic CRC (N = 59) and analyzed for serum IGF-1 and IL-6 by ELISA. Skeletal Muscle Index (SMI) was calculated from cross-sectional image at L3 from computed tomography. Sarcopenia was defined based on published cut points for adults with cancer stratified by body mass index (BMI) as: SMI < 43 cm2/m2 for men and < 41 cm2/m2 for women for normal and underweight; and SMI < 53 cm2/m2 for men and < 41 cm2/m2 for women for overweight and obese. Median and interquartile range (IQR) were reported for patients with sarcopenia versus those without sarcopenia. Spearman and logistic regression were used to examine associations between sarcopenia and serum biomarkers. Results: Median (IQR) age was 62 (49-85). Overall prevalence of sarcopenia was 44% (26/59). The prevalence of sarcopenia was 3% for males (2/59) and 5% for females (3/59) with a BMI < 25 and 27% for males (16/59) and 8% for females (5/59) with a BMI≥25. Median and (IQR) for serum biomarkers in patients with CRC and sarcopenia versus those without sarcopenia were: IGF-1 43 (16) vs. 58.7(27.9) ng/mL (p = 0.007). Correlation between IGF-1 and sarcopenia was (r = -0.4, p = 0.004), but was not statistically significant for IL-6 (r = 0.02, p = 0.88). Both IGF-1 (OR = 0.82, 95% CI 0.69-0.98, p = 0.03) and IL-6 (OR = 0.83, 95% CI 0.70-0.98, p = 0.002) were significant predictors of sarcopenia after adjusting for race and BMI. Conclusions: In this sample of patients with CRC, IGF-1 and IL-6 levels were both lower in patients with sarcopenia compared to those without sarcopenia and levels of both markers predicted the presence sarcopenia.