The work describes an electrochemical sensor for the determination of the tranquilizer clonazepam (CZP) in serum and pharmaceutical preparations. A screen printed carbon electrode (SPCE) was modified with copper nanoparticles anchored on porous silicon (PSi). The surface of the SPCEs modified with the Cu/PSi nanostructure was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoemission spectroscopy, energy dispersive X-ray spectroscopy and field-emission scanning electron microscopy. Cyclic and differential pulse voltammetric methods were used for the electrochemical studies and electrochemical detection, respectively. Several parameters controlling the performance of the modified SPCE were optimized. The peak current values (at a potential of −0.52 V) were used to construct calibration plots. Under the optimum conditions, the calibration plot is linear in the 0.05–7.6 μM CZP concentration range, and the detection limit is 15 nM. The sensor is reproducible, repeatable, highly selective and sensitive. It was successfully applied to the determination of CPZ in spiked serum and in drugs.