In recent years, the excessive use of electronic cigarettes (e-cigarettes), and vaping, as a replacement for traditional tobacco cigarettes, have highlighted potential health risks for users. One such risk is the development of “electronic cigarette (vaping) product use-associated lung injury” (EVALI). This type of lung injury has an unclear cause that may be related to the various components found in e-cigarette fluids. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 or COVID-19) may worsen EVALI symptoms in individuals with both conditions. This could be due to the increased oxidative stress and inflammation caused by e-cigarette use, as research shows increased levels of reactive oxygen species (ROS) and decreased glutathione. In this paper, we present two critical cases of COVID-19 patients with a history of chronic e-cigarette smoking and describe their clinical progression during hospitalization. The findings suggest that their prolonged use of e-cigarettes may have significantly impacted the severity of the disease.