There continues to be a great need for rapid, accurate, and cost-effective point-of-care devices that can diagnose the presence of SARS-CoV-2 virus and development of IgG and IgM antibody responses in early and late stages of COVID-19 disease. Here, we describe a versatile multiplexed electrochemical (EC) sensor platform modified with an antifouling nanocomposite coating that enables single-molecule CRISPR/Cas-based molecular detection of SARS-CoV-2 viral RNA with on-chip signal validation as well as multiplexed serological detection of antibodies against three SARS-CoV-2 viral antigens. The CRISPR-based EC platform achieved 100% accuracy for detection of viral RNA and showed an excellent correlation with RT-qPCR using 30 clinical saliva samples. The serology EC platform obtained 100% sensitivity and 100% specificity for anti-SARS-CoV-2 IgG, as well as 94% specificity and 82% sensitivity for anti-SARS-CoV-2 IgM with 112 clinical plasma samples. These data demonstrate that integration of CRISPR-based RNA detection and serological assays with antifouling nanocomposite-based EC sensors enables performance as good or better than traditional laboratory-based techniques.