Molecular assays from nasopharyngeal swabs are the current reference method to diagnose COVID-19. As an alternative, we evaluated the performance of the iFlash-2019-nCoV Antigen® (YHLO, Shenzhen, China), developed for SARS-CoV-2 N-antigen detection in serum samples. Specificity, determined on 50 pre-pandemic samples, was 100%. Overall sensitivity, evaluated on 40 sera from patients with RT-PCR confirmed infection, was 67.5%. However, sensitivity reached 73% in symptomatic patients, 80% in patients with high and medium nasopharyngeal (NP) viral loads (samples with Ct≤33) and, 90% in samples collected within the first week after symptoms onset. These sera were further analyzed with the COV-QUANTO® ELISA and COVID-VIRO® LFIA assays (AAZ, Boulogne-Billancourt, France). EIA Ag assays from Yhlo and AAZ had comparable performances, and both were more sensitive than the LFIA. These findings suggest that SARS-CoV-2 N-antigen detection in serum could be an alternative to PCR from NP swabs, at least early after onset of symptoms. Further studies are required to confirm these results.