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The coronavirus disease 2019 (COVID-19) is an emerging pandemic caused by a novel coronavirus (SARS-CoV-2). Since December 2019 the new virus has spread all over the world and has become a major health problem also because of the public measures that could affect people’s sexual activity. We report a case of a 35-year-old married male admitted to the andrology outpatient clinic in July 2021 because of sudden onset erectile dysfunction (ED). The diagnostic workup showed no risk factor for ED, normal levels of testosterone, increased levels of endothelial dysfunction markers, such as CRP (C-Reactive Protein) and Endothelin-1, and reduced Vitamin D (VD) levels. Dynamic penile duplex ultrasound (D-PDU) revealed dysfunctional penile arterial flow. The five-item International Index of Erectile Function (IIEF-5) and the Short-Form Health Survey (SF-36) showed a reduction in all domain scores. The patient, initially unresponsive to the high dose oral phosphodiesterase 5 inhibitors (PDE-5is), was treated with vitamin-D and then submitted to LI-SWT (low intensity shockwave treatment), with a progressive clinical benefit at the 12-month follow-up. After 18 months, hormone levels persisted in normal ranges, with a consistent reduction in CRP and Endothelin-1. Additionally, IIEF-5, SF-36 and arterial flow significantly improved over the follow-up period. Thus far, the erectile function was restored and the patient is no more treated with PDE-5i.