Background: While the long-term outcomes of HCT survivors have been described, the acute impact of hospitalization for HCT on patients’ and FC QOL and mood has received little attention. Methods: We conducted a longitudinal study of patients (and FC) hospitalized for HCT. At baseline (6 days pre-HCT), day+1, and day+8 of HCT, we assessed QOL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation FACT-BMT), fatigue (FACT-Fatigue), and mood (Hospital Anxiety and Depression Scale HADS). We used the SF-36 to examine FC QOL [physical component scale (PCS), and mental component scale (MCS)]. Using multivariable linear mixed models, we examined predictors of QOL changes during hospitalization. Results: We enrolled 97% of consecutively eligible patients undergoing autologous (n=30), myeloablative (n=30) or reduced intensity (n=30) allogeneic HCT. Patients’ QOL markedly declined and fatigue increased throughout hospitalization (Table). The proportion of patients meeting criteria for depression (HADS-D > 7) more than doubled from baseline to day+8 (15.6% to 37.8%, P < 0.0001) whereas the proportion of patients with anxiety remained stable (22.2%, P = 0.8). Depression (β= -2.24, F=42.2, p < 0.0001) and anxiety (β= -0.63, F=4.4, p = 0.03) at baseline independently predict worse QOL throughout hospitalization. The FC QOL declined during patient’s hospitalization (PCS: 83.1 to 79.6, P= 0.03, MCS: 71.6 to 67.4, P = 0.04). Conclusions: Patients undergoing HCT reported a rapid and steep deterioration in QOL along with substantially worse fatigue and depression during hospitalization. Greater decrements in QOL were predicted by depression and anxiety highlighting the importance of assessing pre-HCT psychiatric morbidity.