Coronavirus disease 2019 (COVID-19), caused by SARS coronavirus 2 (SARS-CoV-2), is spreading rapidly with no established effective treatments. While most cases are mild, others experience uncontrolled inflammatory responses with oxidative stress, dysregulation of iron and coagulation as features. Lactoferrin, ovotransferrin and lysozyme are abundant, safe antimicrobials that have wide antiviral as well as immunomodulatory properties. In particular, lactoferrin restores iron homeostasis and inhibits replication of SARS-CoV, which is closely related to SARS-CoV-2. Ovotransferrin has antiviral peptides and activities that are shared with lactoferrin. Both lactoferrin and lysozyme are ‘immune sensing’ as they may stimulate immune responses or resolve inflammation. Mechanisms by which these antimicrobials may treat or prevent COVID-19, as well as sources and forms of these, are reviewed.