This retrospective study analyzed three COVID-19 outbreaks in a Serbian nursing home during waves of pre-Alpha, Delta, and Omicron variants. Despite vaccination (mostly BBIBP-CorV) of most residents and staff, outbreaks occurred, with case fatality rates of 31.2%, 9.1%, and 0%, respectively. Older individuals showed a good immune response, preventing significant mortality and morbidity in later outbreaks. The study highlights the impact of SARS-CoV-2 variants and vaccine effectiveness, particularly with BBIBP-CorV.