A highly sensitive method was investigated for the simultaneous determination of acetaminophen (AC), dopamine (DA), and ascorbic acid (AA) using a PbS nanoparticles Schiff base-modified carbon paste electrode (PSNSB/CPE). Differential pulse voltammetry peak currents of AC, DA and AA increased linearly with their concentrations within the ranges of 3.30×10⁻⁸–1.58×10⁻⁴M, 5.0×10⁻⁸–1.2×10⁻⁴M and 2.50×10⁻⁶–1.05×10⁻³M, respectively, and the detection limits for AC, DA and AA were 5.36×10⁻⁹, 2.45×10⁻⁹ and 1.86×10⁻⁸M, respectively. The peak potentials recorded in a phosphate buffer solution (PBS) of pH 4.6 were 0.672, 0.390, and 0.168 V (vs Ag/AgCl) for AC, DA and AA, respectively. The modified electrode was used for the determination of AC, DA, and AA simultaneously in real and synthetic samples.