Herein, a photoelectrochemical aptasensor for the quantitive measurement of the severe acute respiratory syndrome coronavirus-2 receptor-binding domain (Sars-Cov-2 RBD) has been reported for the first time. For this purpose, first, graphitic carbon nitride and (gC3N4) and cadmium sulfide (CdS) quantum dots were fabricated and characterized. After that, gC3N4 and CdS were mixed well. The fabricated nanomaterials were characterized by scanning transmission electron microscopy. Then, the CdS QDs-gC3N4 nanocomposite was added to the solution containing chitosan as an amine-rich polymer to generate a Chitosan/CdS-gC3N4 nanocomposite. Subsequently, the surface of the ITO electrode was modified with Chitosan/CdS-gC3N4. After that, the amine-terminal aptamer probes were immobilized on the surface of the Chitosan/CdS QDs-gC3N4/ITO electrode by using glutaraldehyde as an amine-amine crosslinker. The electrochemical performances of the electrodes were studied using cyclic voltammetry (CV), electrochemical Impedance Spectroscopy (EIS), and photo-electrochemistry (PEC). The surface coverage of the immobilized aptamer probe was founded to be 26.2 pmol.cm(-2). The obtained results demonstrated that the proposed photo-electrochemical aptasensor can be used for the measurement of Sars-Cov-2 RBD within 0.5-32.0 nM. The limit of detection (LOD) was obtained to be 0.12 nM (at 3sigma/slope). The affinity of the Aptamer/Chitosan/CdS QDs-gC3N4/ITO was also founded to be 3.4 nM by using Langmuir-typical adsorption systems. The proposed photo-electrochemical aptasensor was applied for the measurement of the spiked Sars-Cov-2 RBD in human saliva samples at two concentrations. The effect of the interfering biomaterials such as human immunoglobulin G human immunoglobulin A, human immunoglobulin M, and human serum albumin was also studied.