To investigate the impact of thymus on immunological recovery after dose-dense chemotherapy a prospective study of 17 patients diagnosed with diffuse large B-cell lymphoma (DLBCL) was conducted. Patients were monitored before, during and until 3 months after chemotherapy. The thymus was visualized using computer tomographic scans. Patients were divided into two groups according to thymic size, one group comprising of patients without detectable thymus and one group of patients with detectable thymus. Naïve CD4 and CD8 counts were measured by flow cytometry, and to measure thymic output determination of CD4+ cells containing T-cell receptor excision circles (TREC) was done. During chemotherapy, the naïve CD4 count decreased significantly as did the CD4-TREC%. Significant difference in recovery of naïve CD4 counts between patients with detectable and undetectable thymic tissue during treatment with chemotherapy was not found. CD4-TREC% was associated with lower age. It was not possible to demonstrate an association between thymic size and recovery of the naïve CD4+ cells. The study terminated 3 months after the last cycle of chemotherapy, and at that time point the naïve CD4 counts and the CD4-TREC% had not returned to pretreatment levels. However, patients with detectable thymic tissue had higher naïve CD4 counts after the first cycles of chemotherapy, suggesting that these patients may be less susceptible to infectious complications related to chemotherapy.