SARS-CoV-2 is a newly emerged coronavirus that has been widely transmitted since late 2019. It has caused a pandemic and infected roughly 450 million people globally.Hitherto, there is no approved anti-COVID-19 treatment, and vaccination is the only experienced preventive strategy. It mainly promotes the immune system, which is vital as a barrier against COVID-19. Humoral immunity (antibody-mediated immunity), among the various functions of the immune system against the coronavirus, plays an outstanding role in preventing infection. Consequently, we intended to assess IgG and IgM antibodies, 3 and 6 months after infection, to trend their titer and see how long COVID-19 antibodies remained in the human body. According to the research-designed criteria, only 98 patients out of 4500 suspected cases of SARS-CoV-2 infection remained for analysis. Blood samples were taken in three time periods (Day Zero ( T 0 ), 3 and 6 months post-infection) and examined for COVID-19’s IgG and IgM antibodies titration using the ELISA platform. Though both IgG and IgM were still detectable for some subjects at the end of the period, the decline in their levels (from 14.45 ± 5.88 to 2.52 ± 2.33 for IgG [85% decline of antibody titer] and 8.3 ± 0.99 to 0.37 ± 0.14 for IgM [95.5% decline of antibody titer]) was statistically significant ( P value 0.0001). There was no correlation between gender and IgG and IgM levels. Although the levels of both antibodies were overall higher in the senior group (≥ 60 years old), statistical analysis showed a significantly higher level just for IgM in this group ( P value: 0.005). Following the results, although anti-SARS-CoV-2 IgM and IgG antibodies can persist in the blood for 6 months post-infection, their levels steeply declined over time. Therefore, relying on humoral immunity as a trustworthy barrier against SARS-CoV-2 infection calls for more extensive research. Supplementary Information The online version contains supplementary material available at 10.1007/s40995-022-01382-7.