Background:Physical, psychological, and social aspects of health-related quality of life (HRQOL) among head and neck cancer (HNC) survivors may be more affected during the COVID-19 pandemic than before the pandemic. However, the impact is not yet understood well.<br />Methods:Prospectively collected data from the NETherlands QUality of life and BIomedical Cohort study in HNC were used. All patients were diagnosed and treated before the COVID-19 pandemic. Patient reported outcome measures (PROMs) collected 24 and 36 months after treatment (M24 and M36) were compared between survivors who completed both assessments before the COVID-19 pandemic and those who completed M24 before but M36 during the pandemic. Personal, clinical, physical, psychological, social, and lifestyle characteristics of the survivors assessed at baseline or M24 were investigated as potential effect modifiers.<br />Results:In total, 318 HNC survivors were included, of which 199 completed both M24 and M36 before the COVID-19 pandemic and 119 completed M24 before but M36 during the pandemic. Changes in HRQOL between 24 and 36 months follow-up did not differ between the two groups for any of the PROMs. However, in some subgroups of HNC survivors the COVID-19 pandemic negatively affected the course of HRQOL for several PROMs while it positively affected the course of HRQOL for other PROMs.<br />Conclusions:The COVID-19 pandemic did not affect HRQOL in HNC survivors in general, but some subgroups were affected in a positive and others in a negative way.<br />Funding:This work was supported by the Dutch Cancer Society [grant number VU 2013–5930] and the Dutch Cancer Society, Alpe Young Investigator Grant [grant number 12820].