The widespread propagation of SARS-CoV-2 necessitated the development of vaccines, both for healthy individuals and for people with comorbidities. The aim of this article was to present data on the post-vaccination virus-neutralizing response in people living with HIV (PLHIV) in Bulgaria, two months after the second dose of ChAdOx1 S vector vaccine. Totally 40 PLHIV had been vaccinated, 36/40 received a full vaccination course and finally, 32/40 participated in the study. The results were compared to 19 “healthy controls”, also with a completed vaccination protocol. All 32 patients were on antiretroviral therapy at the time of vaccination, most of them (27/32, 84%) had undetectable viral loads and the remaining 5/32 (15%) had a temporary spike up to 400 copies/ml. CD4+ T-lymphocytes counts in 31 of PLHIV group were >350 cells/mm3; one of them had 190 CD4+ T cells/mm3, but this did not affect the antibody response (93.29%). Sera of all participants were tested by blocking ELISA with the “SARS-CoV-2 cPassTM GenScript neutralizing antibody detection kit”. The results expressing the % of neutralization were interpreted as follows: <30% - were considered negative, and those >= 30% - positive. Positive results were also found in the “control” group, where 10/19 examined showed >90% presence of neutralization antibodies. This study confirms the high efficacy of the ChAdOx1S vector vaccine and the excellent humoral response in the PLHIV. The number of patients included in the study is not high, but the results, together with the literature data demonstrate the effectiveness and the need for priority vaccination of PLHIV.