SARS-CoV-2 uses ACE2 receptors (Angiotensin-Converting Enzyme) for entry into the host cell and the transmembrane serine protease 2 (TMPRSS2) for S protein priming. Lactoferrin is endowed with potent antiviral activity, related to its ability to block viral entry into host cells by interacting with viral and/or cell surface receptors. SARS-CoV-2 uses its spike proteins to invade cells via ACE2 receptor. The ability of free and encapsulated LF to prevent binding of SARS-CoV-2 spike protein to HaCaT keratinocytes receptors was evaluated (fluorescent microscopy) through immunostaining with lactoferrin antibody (Cy3-red) and spike protein labeling with Atto48 (green). Untreated control HaCaT cells incubated with the labeled spike protein did not present any red fluorescence due to lactoferrin antibody staining, but a green fluorescence owing to labeled spike protein was observed. Cells treated with 0.001% lactoferrin showed lactoferrin (red) bound cells although Spike protein (green) was not detectable. % 0.0001 LF did not bind most cells (red), whereas spike protein bound cells (Green), but less than the control without product treatment. 0.001% liposomal lactoferrin (LLF) did not show spike binding signal (Green) and high lactoferrin staining was observed (red). LF and LLF prevented the binding of SARS-CoV-2 spike protein to HaCaT cell receptors although at the same concentration LLF was more effective than the free form. LF encapsulation improves the delivery of LF. The liposome by its own structure and composition interact with lipoprotein components of the virus or from cell membranes (TMPRSS2). Oral administration of LLF may be useful in the care of patients with COVID-19 infections.