Introduction and Objectives Clinical and epidemiological data suggest that depression may increase the risk for infection. Infection is a major cause of morbidity and mortality in patients undergoing stem cell transplantation. We investigated the impact of depression on infection rates in patients undergoing autologous or allogeneic stem cell transplant at a single center. Methods We analyzed data from University of California San Diego's Hematopoietic Stem Cell Transplant program to compare outcomes after autologous (n= 472) and allogeneic (n= 259) transplants in patients with hematologic malignancies and with an existing diagnosis of depression versus no depression. Using chi-square testing, we compared the infection rates between patients with or without depression. Results The study included 162 (22.2%) patients with depression versus 568 (77.9%) without depression who underwent allogeneic and autologous stem cell transplant between 2012 and 2017. Using Pearson Chi-square testing, patients with depression had a higher rate of infections (55.6%) versus patients without depression (41%, p=0.001). Depression was associated with multiple infection sites (25% vs 17%, p=0.029), increased risk for bacterial infection (44% versus 28.5%, P Conclusion In our retrospective analysis depression was associated with higher rates of overall infection, bacterial, and fungal infection among hematopoietic transplant patients. Depression was also associated with increased risk for both acute and chronic graft versus host disease. If our observation is confirmed prospectively, then interventions aimed at depression, might improve infection rates in transplant patients.