The prognostic, especially predictive, values of inflammation indexes in advanced colorectal cancer were not established. Therefore, the both values of neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) in patients with initially metastatic colorectal cancer (mCRC) were investigated and compared. Samples were collected from 243 patients who were initially diagnosed with mCRC between 2005 and 2010 in the Sun Yat-sen University Cancer Center. Elevated NLR (p < 0.001), PLR (p = 0.008), and CEA (p < 0.001) were identified as statistically significant poor prognostic factors for overall survival (OS), while only NLR (p = 0.029) and CEA (p < 0.001) were validated as independent predictors. Univariate analysis identified elevated NLR (p < 0.001), PLR (p = 0.023), and CEA (p < 0.001) as statistically significant poor predict factors for the progression-free survival (PFS) of first-line chemotherapy, while NLR (p = 0.013) and CEA (p = 0.001) were independent. In addition, we observed significantly different OS (p < 0.001) and PFS (p < 0.001) among patients who had elevations in both NLR and CEA levels and those having one elevation or neither elevation. NLR, PLR, and CEA were significant predictors of OS and PFS in mCRC. However, only NLR and CEA play as independent. When coupled with CEA, NLR may lead to improved prognostic predictors.