The expansion of electrochemical sensors to biomedical applications at point of care requires these sensors to undergo analysis without any pretreatment or extraction. This poses a major challenge for all electrochemical sensors including electrochemiluminescent (ECL)-based sensors. ECL offers many advantages for biomedical applications; however, obtaining results from complex matrixes has proven to be a large hurdle for the application of ECL sensors within this field. This work demonstrates the potential of cathodic ECL to detect and quantify homocysteine (Hcy) with a 0.1 nM limit of detection, which is associated with hyperhomocysteinemia, in blood. This near-infrared quantum dot (NIR QD)-based ECL sensor displays good linearity allowing for rapid detection and providing a basis for exploitation of ECL-based sensors for biomedical diagnostics utilizing Hcy as a model cathodic coreactant. This work will lay the foundations for future developments in biosensing and imaging fields and stands as an initial proof of concept for the utilization of cathodic ECL technologies for biomedical applications once the limits of detection within clinically relevant levels has been achieved. This work illustrates the potential of cathodic ECL sensors, using Hcy as a model complex, for the detection of biomolecules.