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Background The global coronavirus disease 2019 (COVID-19) pandemic has drastically disrupted cancer care, potentially exacerbating patients’ distress levels. Patients undergoing HSCT may be especially vulnerable to this pandemic stress. However, the associations of the COVID-19 pandemic with distress, fatigue, and QOL are not well understood in this population. Method In a cross-sectional analysis of data from 205 patients undergoing HSCT enrolled in a supportive care trial, we compared baseline pre-HSCT distress (depression, anxiety, and posttraumatic stress disorder [PTSD]) symptoms, fatigue, and QOL between enrollees pre- (i.e., 03/2019-01/2020) and during (i.e., 03/2020-01/2021) the COVID-19 pandemic. We used linear regression models adjusting for sociodemographics and cancer diagnosis to examine the associations between enrollment period and patient-reported outcomes. We used semi-structured qualitative interviews in 20 allogeneic HSCT recipients who were ≥3-months post-HSCT to understand the impact of the COVID-19 pandemic on their recovery post-HSCT. Results Prior to COVID-19, 124 participants enrolled, while 81 participants enrolled during the pandemic. The cohorts had similar baseline demographics and disease risk factors. In multivariate regression models, enrollment during COVID-19 was not associated with pre-HSCT symptoms of depression, anxiety, PTSD, fatigue, or QOL impairment. COVID-19-era participants reported themes of negative (e.g., increased isolation) and positive (e.g., engagement with meaningful activities) implications of the pandemic on HSCT recovery. Conclusions We found no differences in pre-HSCT distress, fatigue or QOL in patients undergoing HSCT prior to or during the COVID-19 pandemic. Patients in early recovery post-HSCT, however, report both negative and positive implications of the COVID-19 pandemic on their lives.

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