Background and Objectives: There are conflicting studies on the prevalence of mediastinal lymphadenopathy (LAP) and its relationship to the prognosis of COVID-19 disease. The prevalence varied from 3.4 to 66 percent and more prevalent in pa- tients who died. This study aimed to investigate the mediastinal lymphadenopathy and the disease progression in COVID-19 patients. Materials and Methods: In this case-control study, 195 COVID-19 patients were divided into two groups, with the medias- tinal lymphadenopathy and without it. In these groups, demographic characteristics, underlying diseases, laboratory results, and outcomes were compared. Results: The median age in the LAP group was higher than the opposite group (62 vs. 58.5; p= 0.037). SpO2 (85% vs. 90%; P <0.001), lymphocyte count (760 vs. 969; p= 0.02), Neutrophil-to-Lymphocyte Ratio (5.53 vs. 4.41; p= 0.02), and ESR (36 vs. 29; p= 0.03) were significantly correlated with the presence of lymphadenopathy, using the Mann-Whitney Wilcoxon rank test. ICU admission (65.71% vs. 36.87; p= 0.003), mechanical ventilation (31.42% vs. 13.75%; p= 0.022), disease se- verity (65.71% vs. 40%; p <0.01), length of hospital stay (9 vs. 7; p= 0.039) and mortality rate (40% vs. 21.25%; p= 0.034) were more predominantly observed in the LAP group, using the χ2 test. There was no apparent difference in sex and the underlying diseases among the two groups. Conclusion: This observation showed a relatively high prevalence of mediastinal lymphadenopathy in COVID-19 patients, which was more common in the elderly with low oxygen saturation. Therefore, LAP may lead to further intensive care needs, more use of mechanical ventilation, high severity of disease, and mortality rate.