AbstractThe widespread accessibility of commercial/clinically‐viable electrochemical diagnostic systems for rapid quantification of viral proteins demands translational/preclinical investigations. Here, Covid‐Sense (CoVSense) antigen testing platform; an all‐in‐one electrochemical nano‐immunosensor for sample‐to‐result, self‐validated, and accurate quantification of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) nucleocapsid (N)‐proteins in clinical examinations is developed. The platform's sensing strips benefit from a highly‐sensitive, nanostructured surface, created through the incorporation of carboxyl‐functionalized graphene nanosheets, and poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) conductive polymers, enhancing the overall conductivity of the system. The nanoengineered surface chemistry allows for compatible direct assembly of bioreceptor molecules. CoVSense offers an inexpensive (<$2 kit) and fast/digital response (<10 min), measured using a customized hand‐held reader (<$25), enabling data‐driven outbreak management. The sensor shows 95% clinical sensitivity and 100% specificity (Ct<25), and overall sensitivity of 91% for combined symptomatic/asymptomatic cohort with wildtype SARS‐CoV‐2 or B.1.1.7 variant (N= 105, nasal/throat samples). The sensor correlates the N‐protein levels to viral load, detecting high Ct values of ≈35, with no sample preparation steps, while outperforming the commercial rapid antigen tests. The current translational technology fills the gap in the workflow of rapid, point‐of‐care, and accurate diagnosis of COVID‐19.