This work efficiently detects uric acid (UA) in a human blood sample using cobalt nanoparticle-immobilized mixed-valent molybdenum sulfide on the copper substrate in a point-of-care (PoC) device. The sensor electrode was fabricated by micromachining of Cu clad boards employing an engraver to generate a three-electrode system consisting of working electrode (WE), reference electrode (RE), and counter electrode (CE). The WE was subjected to physical vapor deposition of mixed-valent MoSx layers by a reaction between Mo(CO)6 and H2S at ∼200 °C using a simple setup following which CoNPs were electrochemically deposited. The RE and CE were covered with Ag/AgCl and Ag paste, respectively. A plasma separation membrane acted as the medium of UA/blood serum delivery to the electrodes. The material and electrochemical characterization confirmed that CoNPs over MoSx provided an enlarged electroactive surface for the direct electron transfer to achieve an enhanced electrocatalytic response. The binary combination of CoNPs and MoSx layers over the Cu electrode reduced the charge-transfer resistance by two times, enhanced the surface adsorption by more than two times, and yielded a high diffusion coefficient of 3.46 × 10–3 cm2/s. These interfacial effects facilitated the UA oxidation, leading to unprecedented mA range current density for UA sensing for the PoC device. The electrochemical detection tests in the PoC device revealed a sensitivity of 64.7 μA/μM cm–2, which is ∼50 times higher compared to the latest reported value (1.23 μA/μM cm–2), a high limit of detection of 5 nM, and shelf life of 6 months, confirming the synergistic effect-mediated high sensitivity under PoC settings. Interference tests confirmed no intervention of similar analytes. Tests on blood samples demonstrated a recovery percentage close to 100% in human serum UA, signifying the suitability of the nanocomposite-based sensor and the PoC device for clinical sensing applications.