Chronic dialysis patients have an increased risk of severe COVID-19 infection-related complications. The aim of this study was to quantify the impact of the COVID-19 pandemic on healthrelated quality of life (HRQoL) and physical activity levels of patients undertaking hemodialysis (HD). This was an observational study that compared data from two periods of time, before the COVID-19 pandemic vs pandemic. We used the Medical Outcomes Survey Short Form (SF-36) to measure the HRQoL and the Human Activity Profile (HAP) questionnaire was used to measure the physical activity. Data were analyzed with a mixed ordinal linear regression. A total of 27 eligible participants were interviewed during COVID-19 pandemic (median age 78 years). The linear regression model showed that the pandemic, after controlling for the covariates age, comorbidity, albumin, and hemoglobin, had a significant impact on the HRQoL. Physical function (􀀀15.7) and social functioning subscales (􀀀28.0) worsened (p = 0.001), and the physical component scale also showed a significant decrease (􀀀3.6; p = 0.05). Time had a significant impact on the Human Activity Profile, with an average activity score diminished with the pandemic (􀀀13.9; p = 0.003). The COVID-19 pandemic had a very negative impact on HRQoL and physical activity level of subjects undertaking hemodialysis. Interventions to improve HRQoL and activity levels of patients undertaking HD are recommended.