SARS-CoV-2 variants pose a significant threat to global public health. However, their influence on disease severity, especially among young adults who may exhibit different clinical characteristics, is debatable. In this retrospective study of 229 young adults hospitalized with COVID-19, we investigated the differences between Poland’s second and third waves of the pandemic. To identify potential predictors of severe COVID-19 in young adults, we analyzed patient characteristics and laboratory findings between survivors and non-survivors and we performed logistic regression to assess the risk of death, mechanical ventilation, and intensive care unit treatment. We found no increase in COVID-19 severity comparing the third and second waves of the pandemic, indicating that the alpha variant had no influence on disease severity. In addition, we found that factors, such as obesity, comorbidities, lung involvement, leukocytosis, neutrophilia, lymphopenia, higher IG count, the neutrophil-to-lymphocyte ratio, C-reactive protein, procalcitonin, interleukin-6, D-Dimer, lactate dehydrogenase, high-sensitive troponin I, creatine kinase-myocardial band, myoglobin, N-terminal-pro-B-type natriuretic peptide, creatinine, urea and gamma-glutamyl transferase, lower estimated glomerular filtration rate, albumin, calcium and vitamin D3, possibly a decrease in red blood cell counts, hemoglobin and hematocrit, and an increase in creatine kinase during hospitalization may be associated with poor outcomes of COVID-19.