Vietnam applied strict quarantine measures to mitigate the rapid transmission of the SARS-COV-2 virus. Central questions were how the COVID-19 pandemic affected health-related quality of life (HRQOL) of the Vietnamese general population, and whether there is any difference in HRQOL among people under different quarantine conditions. This cross-sectional study was conducted during 1 April- 30 May 2020 when the COVID-19 pandemic was at its peak in Vietnam. Data was collected via an online survey using Google survey tool. A convenient sampling approach was employed, with participants being sorted into three groups: people who were in government quarantine facilities; people who were under self-isolation at their own place; and the general population who did not need enforced quarantine. The Vietnamese EQ-5D-5L instrument was used to measure HRQOL. Differences in HRQOL among people of isolation groups and their socio-demographic characteristics were statistically tested. A final sample was made of 406 people, including 10 persons from government quarantine facilities, 57 persons under self-isolation at private places, and the rest were the general population. The mean EQ-VAS was reported the highest at 90.5 (SD: 7.98) among people in government quarantine facilities, followed by 88.54 (SD: 12.24) among general population and 86.54 (SD 13.69) among people in self-isolation group. The EQ-5D-5L value was reported the highest among general population at 0.95 (SD: 0.07), followed by 0.94 (SD: 0.12) among people in government quarantine facilities, and 0.93 (SD: 0.13) among people who did self-isolation. Overall, most people, at any level, reported having problems with anxiety and/or depression in all groups. While there have been some worries and debates on implementing strict quarantine measures can hinder people's quality of life, Vietnam showed an opposite tendency in people's HRQOL even under the highest level of enforcement in the prevention and control of COVID-19.