During COVID‐19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID‐19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39×10−6 mol L−1), response time (8.0±2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma. [ABSTRACT FROM AUTHOR]