SARS-CoV-2 infection susceptibility in dogs and cats has been documented, with identified risk factors contributing to transmission dynamics. Understanding viral prevalence and the evolution of emerging variants across pandemic waves can clarify the potential role of pets as reservoirs. This study evaluated 3298 serum samples (1921 dogs, 1377 cats) collected from 2020 to 2024. Samples were analyzed using ELISA and viral neutralization assays, revealing a positivity rate of 2.7%. We assessed neutralizing antibody titers (nAbs) against the Wuhan-Hu-1 and Omicron BA.1 strains, finding higher titers in felines compared to canines. A marked reduction in samples exceeding the detection limit was observed after November 2022. Longitudinal data from up to 30 months in a dog and 15 months in two cats demonstrated sustained antibody responses, with increased nAb titers in 7 of 14 monitored animals. Multivariable logistic regression of 275 samples indicated that a pet's vaccination status was associated with an increased risk of infection, while spring season, the owner's number of COVID-19 vaccinations, and the owner's vaccination status were protective factors. These results emphasize the significance of vaccination strategies for both human and animal health, supporting the One Health approach.