Background The global emergence of coronavirus disease 2019 (COVID-19) has challenged healthcare and rapidly spread over the globe. Early detection of new infections is crucial in the control of emerging diseases. Evidence of early recorded COVID-19 cases outside China has been documented in various countries. In this study, we aimed to identify the time of SARS-CoV-2 infection circulation by retrospectively analyzing sera of measles patients, weeks before the reported first COVID-19 cases in Angola. Materials and Methods We examined the humoral response against SARS-CoV-2 by using an enzyme-linked immunosorbent assay (ELISA)-based assay on a combined two-step sandwich enzyme immunoassay method. In total, we received 568 study patients with blood specimens collected from 23 September 2019 to 28 February 2020, 442 sera samples that met the criteria of the study were withdrawn and selected from the overall 568 received samples. In this study, we considered seropositives, patients who tested positive for SARS-CoV-2 immunoglobulin G (IgG) and M (IgM) antibodies with the index value >1. Results Of the 442 sera samples that met the criteria of the study, 204 were measles seropositive. Forty out of 204 were confirmed reactive to SARS-CoV-2 viral proteins using IgG and IgM more than 2 weeks before the first reported case in Angola. The humoral response analysis showed significant differences ( p = 0.01) between the IgG and IgM indexes in the unvaccinated measles patients. Similarly, a significant difference ( p = 0.001) was seen between the IgG and IgM indexes in the vaccinated measles patients. Conclusion Here, using the humoral response analysis, we report the identification of early circulation SARS-CoV-2 infection weeks before the first recognized cases in the Republic of Angola.