BACKGROUND: Immunocompromised individuals, hemato-oncologic diseases or post-transplantation included, are, due to impaired immune response, at increased risk for severe and prolonged COVID-19. Observational Studies showed that SARS-CoV-2 RNAemia has been associated with poorer prognosis and higher disease severity. OBJECTIVE: The aim of this study was to investigate the occurrence of RNAemia and its association with anti-SARS-CoV-2 antibodies in immunocompromised COVID-19 patients. Risk factors for RNAemia were included in the analysis. STUDY DESIGN: A retrospective study was conducted in 55 immunocompromised patients tested positive for SARS-CoV-2, who received treatment with monoclonal antibodies (mAb) between December 2021 and March 2022. Serological and virological tests were performed before mAb administration and clinical data were collected from electronic health records. RESULTS: Out of 55 patients, 35 % showed SARS-CoV-2 RNAemia. RNAemia was present in the 2 reported fatal cases. It was associated with negative testing for anti-receptor binding domain (RBD) IgG, anti-S2 domain of spike protein (S2) IgG and a lower leukocyte count. No association was found between previous COVID-19 vaccinations and the risk for RNAemia in immunocompromised patients. CONCLUSION: The study underscores the importance of humoral response in controlling SARS-CoV-2 replication. RNAemia can serve as a potential biomarker for disease severity in immunocompromised individuals. Therefore, it should be considered in clinical settings for appropriate therapy decisions. Further research is needed to evaluate the pathophysiology and implications of RNAemia in immunodeficient patients with COVID-19.