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Background: The COVID-19 pandemic in Brazil led to the suspension of face-to-face classes. However, the importance of continuing this activity made it necessary to return to these activities. This study assessed COVID-19 cases at a university in Brazil before and after the return to face-to-face classes. Methods: This study evaluated the positivity rate of COVID-19 cases through antigen testing over two years (April 2021–23) in a group of students and university staff in northeastern Brazil. Results: We found that of the 2,635 tests performed, 711 (27.0 %) had a detectable result throughout the period. We found no differences between the viral presence and age group, presence of symptoms, or position at universities (students or staff). Males had a greater tendency to present a detectable result compared to women. January, February, and July, 2022 show an increase in detected cases compared to other months. This result follows the national increase in cases caused by the Omicron (B.1.1.529) variant and its subvariants (BA.1, BA.1.1, BA.2, and BA.3) circulating in Brazil in these months. Conclusions: Our study makes it possible to monitor active cases of COVID-19 at a time when new variants are emerging and classes are resuming, contributing to the safety of the academic community and minimizing the viral impact on the return to classes in the institution.