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Summary Objectives We report the biological and clinical impacts possibly associated with HHV-6 reactivation in autologous hematopoietic stem cell transplant (AHSCT) recipients after intensive chemotherapy regimen for lymphoma. Methods We retrospectively reviewed clinical, biological, radiological, treatment and outcomes of patients with positive HHV-6 DNA in whole blood following autologous hematopoietic stem cell transplantation. Results Blood HHV-6 reactivation was reported in 27 (8.5%) patients among 316 AHSCT recipients after high dose therapy for lymphoma. Thirteen (4.1%) patients were symptomatic with fever (100%), diarrhea (61.5%), skin rash (46.1%), and pneumonia (23.1%). Antiviral treatment was administered in 9 (69%) patients and outcome was favorable in all cases. Conclusion Our study suggests a possible pathogenic role of HHV-6 in AHSCT recipients and suggests an impact of antiviral treatments on viral replication and clinical signs resolution.