Influenza A viruses (IAVs) are among the most common sources of new pandemic strains in humans. Spillover from birds to mammals can lead to viral adaptation in new hosts, as seen with IAV H5N1. H5N2 viruses have also been transmitted successfully to humans through contact with infected birds and poultry. In the present study, we evaluated the presence of antibodies against H5Nx viruses in serum samples from a Mexican adult population (n = 476) using the hemagglutination inhibition (HI) test. The analysis included comparisons between sex and age groups. Potential epitopes recognized in the H5 proteins of each strain were predicted using Ellipro. We detected antibodies against H5N1 in 2.5% of the samples, with the highest HI titers of 1:64. The proportion of positive samples for H5N2 2006 was higher (18.9%) than for H5N2 2024 (10.7%). The oldest groups (>50 years old) showed the highest proportion of positives for both viruses, whereas the youngest was for H5N1. These results demonstrate a low proportion of cross-reactive antibodies against the IAV H5N1.