Severe acute respiratory syndrome (SARS)-CoV-2 virus causes novel coronavirus disease 2019 (COVID-19), and there is a possible role of oxidative stress in the pathophysiology of the disease. Excessive oxidative stress could be responsible for the alveolar damage, thrombosis, and other organ damage observed in COVID-19. Oxidative stress has been linked to multi-organ failure. This meta-analysis discusses the role of oxidative stress associated with SARS-CoV-2 and the mechanisms involved. Subsequently, PubMed, Scopus, and Google Scholar databases were searched till June 2022, using suitable keywords to fill in the scientific lacuna.  The SARS-CoV-2 virus interacts with multiple Toll-like receptors (TLRs), including TLR4, which activate the nuclear factor kappa B (NFkB) pathway. The activation of this pathway initiates transcription of pro-inflammatory cytokines, which causes the well-known symptom of cytokine storm which is associated with severe COVID-19. The pro-inflammatory cytokine storm creates a positive feedback loop that ultimately increases oxidative stress throughout the body. The central nervous system (CNS) is affected by this increase in oxidative stress related to COVID-19 as seen in patients presenting with ‘brain fog’ and/or an Alzheimer’s-like phenotype associated with COVID-19. Furthermore, the various therapeutics implicated in treating COVID-19 and the oxidative stress that contributes to the etiology and pathogenesis of COVID-19 are discussed. Further mechanistic and clinical research to combat COVID-19 is warranted to understand the exact mechanisms, and its true clinical effects need to be investigated to minimize complications from COVID-19.