Introduction Studies about the duration of the humoral and cellular response following the bivalent booster administration are still scarce. We aimed at assessing the humoral and cellular response in a cohort of healthcare workers that received this booster. Material and methods Blood samples were collected before the administration of the bivalent booster from Pfizer-BioNTech and after 14, 28, 90, and 180 days. Neutralizing antibodies against either the D614G strain, the delta variant, the BA.5 variant, or the XBB.1.5 subvariant were measured. The cellular response was assessed by measurement of the release of interferon gamma (IFNγ) from T cells in response to an in vitro SARS-CoV-2 stimulation. Results A substantial waning of neutralizing antibodies was observed after 6 months (23.1‐fold decrease), especially considering the XBB.1.5 subvariant. The estimated T _1/2 of neutralizing antibodies was 16.1 days (95% CI=10.2–38.4 days). Although most participants still present a robust cellular response after 6 months (i.e., 95%), a significant decrease was also observed compared to the peak response (0.41 versus 0.95 UI/L, p=0.0083). Conclusion A significant waning of the humoral and cellular response was observed after 6 months. These data can also help national competent authorities in their recommendation regarding the administration of an additional booster.