The pandemic of Coronavirus Disease 2019 (COVID-19) has a significant impact on older individuals, those with comorbidities, and a bias toward males. Mortality, associated with an exacerbated immune response by proinflammatory cytokines, suggests potential hormonal influences in this scenario. The objective of this research was to analyze the expression of Estrogen Receptor α (ERα), Estrogen Receptor β (ERβ), G Protein-Coupled Estrogen Receptor (GPER), and the Angiotensin-Converting Enzyme 2 (ACE2) receptor, as well as their relationship with the viral load of SARS-CoV-2 and serum cytokine levels in three demographic groups of unvaccinated individuals diagnosed with COVID-19: premenopausal women, postmenopausal women, and men. The presence and expression of ERα, ERβ, and GPER, along with the ACE2 receptor, were analyzed by immunofluorescence assays in cells obtained from nasopharyngeal swabs of individuals with confirmed COVID-19 through RT-qPCR testing. Additionally, serum cytokine levels were evaluated using a chemiluminescent microparticle immunoassay. The results highlighted notable disparities in the expression of ERα and ACE2, as well as a higher expression of IL-8 and MIP-1β in the premenopausal women group compared to postmenopausal women and men. These findings suggest that in premenopausal women with COVID-19, the elevated expression of ERα and ACE2 could play a protective role, strengthening the antiviral immune response. The importance of exploring the complex hormonal and molecular influences in the pathogenesis of COVID-19 is emphasized, underscoring the need for additional research to better understand the factors determining severity and immune response in different demographic groups.