Amplification of viral ribonucleic acid by real-time reverse transcriptase polymerase chain reaction is the gold standard to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, alternative reliable, fast, and cost-effective methods for the detection of SARS-CoV-2 are still needed. In this chapter, the mass spectrometry-based detection of amplified polymerase chain reaction products of SARS-CoV-2 genes from oral or nasopharyngeal swabs is described. The respective SARS-CoV-2 test has previously been shown to meet standard quality criteria and was therefore approved by the authorities in Europe and the USA.