Objective To explore the correlation of protein and mRNA levels of monocyte chemotactic protein-1 (MCP-1) and serum amyloid A protein (SAA) with cognitive function in chronic obstructive pulmonary disease (COPD) patients with or without hypoxemia, in order to identify the serum indexes of early cognitive impairment in patients with COPD, and investigate the effect of hypoxemia on cognitive impairment. Methods Sixty-two COPD patients admitted in the respiratory department of Affiliated Hospital of North China University of Science and Technology from January 2013 to January 2017 were included in the study. The COPD patients were divided into a hypoxemia group (25 cases) and a non-hypoxemia group (37 cases) according to blood gas analysis. Meanwhile 30 healthy subjects were recruited as control. ELISA was used to measure the concentration of serum MCP-1 and SAA in all subjects, and RT-PCR was used to detect the mRNA expression of MCP-1 and SAA in peripheral blood mononuclear cells. Montreal cognitive assessment scale (MoCA scale) was used to determine cognitive function. The expression levels of MCP-1 and SAA were compared between three groups, and the correlations with cognitive dysfunction were analyzed. Results The expression levels of serum MCP-1 and SAA had the same trend as those of MCP-1 mRNA and SAA mRNA in peripheral blood in the COPD patients. The protein and mRNA levels of MCP-1 and SAA were higher than those in the healthy control group (all P<0.05). The COPD hypoxemia group and the COPD non-hypoxemia group were lower than the control group in MoCA score, and the MoCA score of the COPD hypoxemia group decreased more obviously (allP<0.05). The protein and mRNA levels of SAA and MCP-1 were negatively correlated with MoCA score (allP<0.05). Conclusion The protein and mRNA levels of MCP-1 and SAA in peripheral blood increase in COPD patients, and hypoxemia may be involved in cognitive dysfunction in COPD patients.