Prompt diagnosis and prevention from coronavirus disease (COVID-19), a highly contagious infection, are critically required. While PCR testing is effective, it is costly, painful, and time-consuming. Alternatively, breath analysis for detecting COVID-19 provides a cost-effective and instant diagnostic approach. COVID-19 infected patients exhale ethyl butyrate (EB) as a biomarker of the infection. This study explores the doping of C20 fullerene with alkali metals to enhance its ability to detect ethyl butyrate. EB was weakly adsorbed onto C20 and strong adsorbed on doped fullerenes (M@C20) with maximum adsorption energies of −27.66 kcal/mol for Li@C20. QTAIM and IRI analyses confirmed Van der Waals interactions between EB and M@C20. NBO and MEP analyses provided evidence of charge transfer from the biomarker towards the M@C20. This charge transfer decreased the carbonyl bond stretching frequency from 1838 cm−1 to 1772, 1782, and 1788 cm−1 in three complexes (EB−Li@C20, EB−Na@C20, and EB−K@C20), respectively. This IR analysis supports the potential application of doped fullerenes in infrared-based detectors. Absorption maxima (λmax) were calculated as 534 nm (green), 594 nm (yellowish orange), and 587 nm (yellow) for three complexes. These shifts indicate potential application of M@C20 in naked-eye detectors. The shortest recovery time was 2.9 × 10−11 s for K@C20, suggesting it a suitable reusable sensor. These findings enable the development of fullerene-based sensors for both naked-eye and infrared-based detection of COVID-19.