Background: A growing body of evidence indicates gender difference in the severity of COVID-19.Objectives: The aim of the present study is to highlight gender difference regarding symptoms, laboratory investigations, complications, and outcome parameters of COVID-19 in admitted cases during the first wave of the disease. Methods: A cross sectional retrospective descriptive epidemiological approach was carried out using electronic patients’ records review. Results: One thousand and one hundred fifty males (77.6%) and 332 females (22.4%) cases for COVOD-19 were subjected to the final analysis. The proportions of general body ache, loss of smell and sore throat were significantly higher among females (13.9%, 2.7% and 15.7%) than males (9.9%, 0.3% and 11.0%), whereas shortness of breath was significantly higher in males than females. A significantly higher proportion of women were more likely to suffer from low ferritin level than men, whereas men were more likely to suffer from a low lymphocytic count. Also, a higher proportion of males suffered from high levels of creatinine than females. No significant difference between males and females regarding COVID-19 complications except for respiratory complications that were more significantly encountered among males than females. Not only more males (11.9%) tended to use oxygen therapy than females (7.2%) but they used it through nasal masks (54% compared with 29.2%) and at a higher flow rate (26.3% compared with 8.3% at a flow rate more than 10 L/min). A higher percentage of male cases then females required to be admitted to the ICU significantly (p < 0.001) as 9.7% of males needed care in the intensive care units (ICU) compared with only 3.3% of females. Conclusions: There is a difference of COVID-19 presentation, severity, and hospitalization, between men and women. Overall, this renders males to be at a higher risk for severe forms of the COVID-19 disease especially with regard to respiratory complications.