Updated project metadata. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not only exerts a deep impact over the respiratory system, but it also affects the cardiovascular system, causing vascular damage and thromboembolic events in critical patients. The endothelial dysfunction taking place in response to COVID-19 represents one of the first steps in this cascade of events that might leads to long-term sequelae over the vascular function. However, despite the enormous efforts in the last two years, the molecular mechanisms involved in such processes remains poorly understood. Using a label free-quantitative proteomics approach, we profiled the proteome of endothelial colony forming cells (ECFCs), after its incubation with the serum from individuals infected with COVID-19, whether asymptomatic or critical patients. Specifically, ECFCs were incubated ex-vivo with the serum of either SARS-CoV-2 negative donors (PCR-/IgG-), SARS-CoV-2 positive asymptomatic donors, at different infective stages: PCR+/ IgG- and PCR-/IgG+, or hospitalized critical COVID-19 patients, followed by mass spectrometry analysis. Remarkably, in response to all infected serums, the differentially expressed protein were found to be correlated with alterations in viral infection, RNA metabolism or autophagy, among others. Moreover, the serum of critical patients promoted the highest number of protein alterations, many of which associated with cardiovascular related pathologies. Finally, machine learning algorithms confirmed the discriminating potential of some proteins differentially expressed between conditions.