Background: Vascular endothelial growth factor (VEGF) reportedly plays an important role in the progression of malignant neoplasms, and have been reported to induce myeloid-derived suppressor cells (MDSC) that appears in cancer and inflammation. Methods: Blood samples were collected from 57 patients, including 8 with esophageal cancer, 20 with gastric cancer, 29 with colorectal cancer, and from 18 healthy volunteers. We measured serum concentrations of VEGF and analyzed correlations with nutritional damage, immune suppression and systemic inflammation. As markers of immune function, IL-12 production of PBMC and MDSC (CD 11b⁺, CD14^-, CD33⁺) were measured. Serum concentrations of albumin and rapid turnover protein were measured as a marker of nutritional status. Results: A significant increase in serum levels was seen in patients with esophageal, gastric, and colorectal cancers compared to healthy volunteers. Levels of VEGF were inversely correlated with serum concentrations of albumin, prealbumin and retinol-binding protein. Serum concentrations of VEGF were inversely correlated with the production of interleukin (IL)-12 and correlated with MDSC. VEGF levels also correlated with neutrophil count and neutrophil/lymphocyte count, and correlated inversely with lymphocyte count. Serum VEGF levels were then divided about a cutoff of 500 pg/ml, with levels of prealbumin and retinol-binding protein significantly decreased in patients with higher VEGF levels. Stimulation index and IL-12 production were significantly decreased in the group with higher VEGF levels, and MDSC counts tended to be higher in this group. Conclusions: These results demonstrated that increased production of VEGF correlated with systemic inflammation, nutritional impairment and inhibition of cell-mediated immunity involving MDSCs. An inactivation of dendritic cells may be occurring by the activation of MDSC. Anti-VEGF therapy may be of importance in treating digestive system cancers.