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The reverse transcriptase polymerase chain reaction (RT-PCR) performed on nasopharyngeal (NP) swabs still remains the gold standard method for the diagnosis of SARS-CoV-2 infection [1]. The interest of measuring the nucleocapsid (N) SARS-CoV-2 antigen in blood has been investigated in some studies [2–5] but determination of the spike (S) antigen in blood received little attention. The aim of this study was to evaluate the clinical performance of two antigen assays for N and S performed in the same analytical platform and technology in blood of SARS-CoV-2 infected patients. The relationship between antigens and disease severity was also investigated. A total of 81 unvaccinated patients with a documented molecular diagnosis of SARS-CoV-2 infection were included between April and July 2021. For each patient, a blood sample was obtained within 12 h of the NP sampling (median delta time= 1 min, IQR …