Growing research data suggests that the severity of COVID-19 is linked with higher levels of inflammatory mediators, such as cytokines, chemokines, tumor necrosis factor, C-reactive protein, ferritin, and D-dimers. In addition, it was evident from the existing research data that the severity of SARS-CoV-2 infection differs according to independent risk factors such as race and ethnicity. Some scarce evidence shows that the European Roma community is likely to be at an elevated risk of illness and death during the pandemic due to their lifestyle, social factors, and economics. Assuming that precautions must be taken to protect this population from coronavirus infections and from widening existing disparities in comparison with the Romanian ethnic population, the current study aimed to observe the clinical evolution of the Roma patients with severe SARS-CoV-2 infection in correlation with the laboratory findings and inflammatory markers involved. After calculating the sample size requirements, we included 83 Roma patients admitted to the hospital with severe COVID-19 and 236 patients of Romanian ethnicity with the same inclusion criteria. Patients were selected from the period stretching from March 2020 to December 2021, before COVID-19 vaccines were introduced. Compared with the general population, the Roma patients with severe SARS-CoV-2 infection had a higher unemployment rate (39.8%), and most of them were residing in rural regions (65.4%). There were significantly more overweight patients in the Roma group than in the control group (57.8% vs. 40.7%), and it was also observed that high blood pressure and diabetes mellitus were significantly more prevalent in the Roma patients. They had significantly longer mean duration of hospitalization was significantly longer in the group of Roma patients (18.1 days vs. 16.3 days). IL-6 and CRP levels were significantly more elevated during admission in the group of Roma patients (43.4% vs. 28.4%); however, IL-6 levels normalized at discharge, but ESR remained high. Although ICU admissions were significantly more frequent in this group, the mortality rate was not significantly higher than in the general population. It is necessary to plan different healthcare strategies aimed at special populations, such as the Roma ethnicity to prevent disparities in negative outcomes reflected in this study. The results imply that community-health collaborations between organizations of minority groups and healthcare professionals can mitigate the disproportionate consequences of the pandemic on Roma.