Abstract Increasing evidence suggests that the human blood hosts microbes including bacteria and eukaryotic viruses, which could have important implications for health. Bacteriophages of the blood are challenging to study and have been overlooked, but could translocate to this environment from different body-sites. We thus developed specific virome protocols and analysis methods to study the viral communities of blood samples obtained from healthy individuals and Crohn’s disease (CD) patients. We uncovered a diverse viral community in the human blood, dominated by phages infecting Pseudomonadota bacteria. We found that an important fraction of those phages overlaps with the gut virome, consolidating the idea that gut phages can translocate to the blood. Strikingly, viral communities of the blood were different between CD patients and healthy individuals, revealing a new signature of disease. This was not the case for fecal viral communities. Collectively, these results advance our knowledge of the microorganisms present in the human blood and pave the way for further studies of this environment in the context of disease.