Spontaneous epistaxis in patients with COVID-19 can represent a clinical challenge with respect to both the risk of contamination and the treatment options. We herein present the data of 30 patients with COVID-19 who developed spontaneous epistaxis while hospitalized at Eastern Piedmont Hospital during March and April 2020. All patients received low-molecular-weight heparin during their hospital stay and required supplementary oxygen therapy either by a nasal cannula or continuous positive airway pressure. Both conditions can represent risk factors for developing epistaxis. Prevention of crust formation in patients with rhinitis using a nasal lubricant should be recommended. If any treatment is required, appropriate self-protection is mandatory.