Human coronavirus NL63 (HCoV-NL63) is a species of coronavirus, specifically a Setracovirus from among the Alphacoronavirus genus. It was identified in late 2004 in a seven-month-old child with bronchiolitis in the Netherlands. The virus is an enveloped, positive-sense, single-stranded RNA virus which enters its host cell by binding to ACE2. Infection with the virus has been confirmed worldwide, and has an association with many common symptoms and diseases. Associated diseases include mild to moderate upper respiratory tract infections, severe lower respiratory tract infection, croup and bronchiolitis.

The virus is found primarily in young children, the elderly, and immunocompromised patients with acute respiratory illness. It also has a seasonal association in temperate climates. A study performed in Amsterdam estimated the presence of HCoV-NL63 in approximately 4.7% of common respiratory illnesses. The virus originated from infected palm civets and bats. Estimates of its divergence from another coronavirus (HCoV-229E) are around 1000 years ago; it has likely circulated in humans for centuries.

The evolution of HCoV-NL63 appears to have involved recombination between an ancestral NL63-like virus circulating in African Triaenops afer bats and a CoV 229E-like virus circulating in Hipposideros bats. Recombinant viruses can arise when two viral genomes are present in the same host cell.