Here, we reported the synthesis of reduced porous graphene oxide (rPGO) decorated with gold nanoparticles (Au NPs) to modify the ITO electrode. Then we used this highly uniform Au NPs@rPGO modified ITO electrode as a surface-enhanced Raman spectroscopy-active surface and a working electrode. The uses of the Au nanoparticles and porous graphene enhance the Raman signals and the electrochemical conductivity. COVID-19 protein-based biosensor was developed based on immobilization of anti-COVID-19 antibodies onto the modified electrode and its uses as a probe for capturing the COVID-19 protein. The developed biosensor showed the capability of monitoring the COVID-19 protein within a concentration range from 100 nmol/L to 1 pmol/L with a limit of detection (LOD) of 75 fmol/L. Furthermore, COVID-19 protein was detected based on electrochemical techniques within a concentration range from 100 nmol/L to 500 fmol/L that showed a LOD of 39.5 fmol/L. Finally, three concentrations of COVID-19 protein spiked in human serum were investigated. Thus, the present sensor showed high efficiency towards the detection of COVID-19.