Coronavirus Disease 2019 [COVID-19], caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV2], has rapidly evolved into a global health emergency. Neopterin [NPT], produced by macrophages when stimulated with interferon [IFN-]gamma, is an essential cytokine in the antiviral immune response. NPT has been used as a marker for the early assessment of disease severity in different diseases. The leading cause of NPT production is the pro-inflammatory cytokine IFN-. Macrophage activation has also been revealed to be linked with disease severity in SARS-CoV-2 patients. We demonstrate the importance of NPT in the pathogenesis of SARS-CoV-2 and suggest that targeting NPT in SARS-CoV-2 infection may be critical in the early prediction of disease progression and provision of timely management of infected individuals.