Background: COVID-19 increased health inequalities worldwide. Even among healthcare workers, social-economical features enhanced the risk of infection (having positive serology) during the first outbreak. The Omicron variant changed the pandemic course and differs from previous variants in many aspects (molecular, clinical, and epidemiological). Herein, we investigated if the profile of our hospital SARS-CoV-2-positive workers during the Omicron outbreak was the same as the first COVID-19 wave. Methods: Socio-demographics, previous infection, and vaccine status of 351 healthcare workers from our institution during the Omicron outbreak were compared between SARS-CoV-2-negative and -positive workers, using chi-square tests. These data were confronted with the profile observed at the beginning of the pandemic. Results: Compared to the original COVID-19 wave, higher odds of SARS-CoV-2 positivity in highly exposed workers in our hospital and a loss of impact of public transportation and other socio-demographic features in SARS-CoV-2 transmission were observed. Conclusions: Our data suggest the current phase of the pandemic is associated with a reduction of social inequalities among healthcare workers in Rio de Janeiro, possibly due to vaccine-associated protection. Therefore, a worldwide effort to advance vaccination coverage, especially for healthcare workers in developing countries, should be reinforced.