A highly sensitive nonenzymatic electrochemical sensor was fabricated for glucose determination based on CuO nanoparticles decorated carbon spheres (CuONPs-CSs). CuONPs-CSs was prepared by an in situ precipitation procedure. CuONPs-CSs was characterized by transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy and electrochemical impedance spectroscopy. The CuONPs-CSs modified glassy carbon electrode showed enhanced electrocatalytic activity toward the oxidation of glucose in alkaline media, and a nonenzymatic glucose sensor was constructed based on the functional composite modified electrode. Under optimal experimental conditions, the designed sensor showed a fast response to glucose with a good linear concentration range from 5.0 x 10(-7) to 2.3 x 10(-3)M, a high sensitivity of 2981 mu A mM(-1) cm(-2) and a limit detection of 0.1 mu M at the signal-to-noise ratio of 3. This sensor showed good accuracy, acceptable precision and reproducibility. The sensor was highly selective to glucose in the presence of commonly interfering species like ascorbic acid, dopamine, uric acid and chloride ion, and successfully applied to analyze glucose concentration in human serum samples. (C) 2015 Elsevier B.V. All rights reserved.