Purpose: This study aims to assess the effect of the COVID-19 confinement on the population wellbeing using the EQ-5D questionnaire. Methods: After receiving the written permission from the EuroQol Research Foundation, an online-based survey was prepared and a total of 1380 participants were recruited via social media. The relationships of all the factors were studied as well as the scores of the EQ-5D including EQ-5D Index, Visual Analogue Scale (VAS), and each of the EQ-5D dimension. Linear regression for the Index and VAS and Logistic regression model were used to examine each dimension. Results: The median EQ-5D Index and VAS scores were 0.65 (0.5-0.75), 80 (60-90), respectively. The most frequently reported problem was anxiety/depression (67.3%), followed by usual activities (48.6%). The statistical analysis showed that factors significantly associated with more reported problems in at least one EQ-5D dimension (P<0.05) were: females, aging, being unmarried, low income, school studies, living in refugee camps, and villages, unemployment, having chronic diseases or pain, and obesity. It is important to note that participants responded in November showed more problems compared to December-2020. On the other hand, more problems were reported by participants who were infected, had known affected persons, had no enough information, perceived negative effect of confinement, and those indicated having a high infection chance (P<0.05). Conclusions: This work provides important evidence on the health status and wellbeing during the COVID-19 confinement in a sample of the Palestinian population, affecting almost all the aspects of the health state and wellbeing. This effect could be minimized by improving the COVID-19 preventive education and monitoring that can play an important role in all health and life aspects among the Palestinian population in facing this pandemic.