In the context of COVID-19 outcomes, global data have deduced a gender bias towards severe disease among males. The aim is to compare morbidity and mortality during two years of the COVID-19 pandemic in female and male patients with COVID-19, as well as to assess length of stay, time of health-seeking behavior after positive diagnosis, and vaccination differences. A retrospective-archive study was conducted in Israel from 1 March 2020 to 1 March 2022 (two consecutive years). Data were obtained from the Israeli Ministry of Health’s (MOH) open COVID-19 database. The findings indicate female infections are 1.12 times more likely, across almost all age groups, apart from the youngest (0–19) age groups. Despite this, the relative risk of severe illness, intubation and mortality is higher among men. In addition, our findings indicate that the mean number of days taken by unvaccinated men from positive diagnosis to hospital admission was greater than among unvaccinated women among the deceased population. The findings of this study reveal lessons learned from the COVID-19 global pandemic. Specifically, the study shows how human biological sex may have played a role in COVID-19 transmission, illness, and death in Israel. The conclusions of this study indicate that targeted approaches, which take into consideration sex and gender and the intersecting factors are necessary to engage in the fight against COVID-19 and ensure the most effective and equitable pandemic response.