The study describes the application of CuO nanostructures as an effective electrode modifying material for the direct electrocatalytic oxidation of N-acetyl-L-cysteine (NAC). The CuO nanostructures were synthesized using hydrothermal growth method with the assistance of NAC, adipic acid (AS) and citric acid (CA) utilized as effective growth modifiers. The morphological characterization of the as-synthesized nanostructures reveled formation of highly distinct and attractive structural features signifying the efficient growth controlling and directing capabilities of the used modifiers. Although, all the fabricated nanostructures were known to possess electrocatalytic potential for the oxidation of NAC. However, the CA modified CuO nanostructures were noted to demonstrate greater sensitivity compared to its other competitors. The developed sensor system relies on the relatively high electro-active area and charged moieties associated with the surface of CA assisted CuO, thus creating a favorable environment for the faster diffusion of analyte towards catalyst surface. The developed sensor exhibited excellent working linearity in the selected concentration range of 0.1 to 5.0 mu M with estimated LOD value of 0.01 mu M. (C) 2016 Elsevier B.V. All rights reserved.