Purpose. The COVID-19 pandemic has overwhelmed many healthcare systems. Seasonality is a feature of several infectious diseases. Studies regarding the association of seasonal variations and COVID-19 have shown controversial results. Therefore, we aimed to compare COVID-19 characteristics and survival outcomes between the fourth and fifth waves in Iran, which corresponded to spring and summer, respectively. Methods. This is a retrospective study on the fourth and fifth COVID-19 waves in Iran. One hundred patients from the fourth and 90 patients from the fifth wave were included. Data from the baseline and demographic characteristics, clinical, radiological, and laboratory findings, and hospital outcomes were compared between the fourth and fifth COVID-19 waves in hospitalized patients in Imam Khomeini Hospital Complex, Tehran, Iran. Results. The fifth wave patients were more likely to present with gastrointestinal symptoms than the patients from the fourth wave. Moreover, patients in the fifth wave had lower arterial oxygen saturation on admission (88% vs. 90%;
P
=
0.026
), lower levels of WBCs (neutrophils and lymphocytes) (6300.00 vs. 8000.00;
P
=
0.004
), and higher percentages of pulmonary involvement in the chest CT scans (50% vs. 40%;
P
<
0.001
). Furthermore, these patients had longer hospital stays than their fourth-wave counterparts (7.00 vs. 5.00;
P
<
0.001
). Conclusions. Our study indicated that patients in the summer COVID-19 wave were more likely to present with gastrointestinal symptoms. They also experienced a more severe disease in terms of peripheral capillary oxygen saturation, percentages of pulmonary involvement in CT scans, and length of hospital stay.