question: Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID‐19. Our objective was to investigate health‐related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID‐19 pandemic. A cross‐sectional survey of adult SOT recipients undergoing follow‐up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ‐5D‐5L, Short‐Form Mishel Uncertainty‐in‐Illness scale (SF‐MUIS) and Brief Cope, respectively. Interactions with COVID‐19 risk perception, access to healthcare, demographic and clinical variables were assessed. The survey was completed by 826 of 3,839 (21.5%) invited participants. Overall, low levels of uncertainty‐in‐illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self‐perceived susceptibility to COVID‐19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to healthcare, a perceived high risk of severe COVID‐19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies were associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.