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Background: From sepsis to COVID-19-induced multi-organ failure, inflammation and immune system activation play an important role. It has been argued that inflammation and over-activation of the immune system could be mediating a pro-oxidant microenvironment that can induce cytotoxic effects that potentiate tissue damage favoring organic deterioration. Aims: To investigate whether induction of oxidative stress by COVID-19 infection could inhibit mitochondrial function and cause cellular damage in leukocytes. Methods: We evaluated plasma levels of nitric oxide, hydrogen peroxide and protein carbonylation using spectrophotometry, in addition to evaluating mitochondrial function and cell death by fluorescence microscopy and leukocyte morphology, in COVID-19 patients at two time points: viremia and severe sepsis with multi-organ failure. Results: COVID-19 induces increased oxidative stress markers that activate cellular damage processes. In the viremia stage, was observe with an increase in peroxide (28.9%), nitric oxide (370.3%) and carbonylated proteins (61.8%), which was correlated with an increase in inhibition of mitochondrial function (66%), early apoptosis (212%) necrosis (405%), and leukocytes-reactivity. The severe sepsis stage with multi-organ failure also showed a further increase in levels of peroxide (46.4%) with a slight decrease in nitric oxide (216.2%) but with more carbonylated proteins (102%), regarding what was observe in viremia. This oxidative process was correlate with less inhibition of mitochondrial function (32.4%) and an increase in late apoptosis (463%), and morphology changes evidencing damage in the leukocytes. Conclusion: SARS-CoV-2 induced damage promotes levels of oxidative stress markers and mitochondrial dysfunction that potentiate morphological changes and cell death in leukocytes. These cellular effects could be integrating into the physiopathology of COVID-19. These processes explain the rapid changes in the immune system, and that present an initial over-activation and early massive death due to SARS-CoV-2 infection, promoting endothelial-alveolar damage that would cause multi-organ failure. WHAT'S KNOWN? (what is already known about this subject?)Current research indicates that SARS-CoV-2 infection induces various processes of cellular damage mediated by inflammation derived from the activity of the immune system, and that these events potentiate cellular damage in various tissues such as the endothelium, lungs, heart, etc. In severe cases, it has been indicated that patients have leukopenia, however, the effect of the infection on the cells of the immune system and in the early stages of the disease has not been evaluated. WHAT'S NEW? (what does this study contribute to the literature?)Our results show the effects of SARS-CoV-2 infection on mitochondrial function and cell damage in early stages, specifically in leukocytes as a fundamental population that must mediate the damage induced by the infection, and that responds to the inductive effect. of oxidative stress. So it propo...