The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus initially appeared in Wuhan, Hubei Province, China has caused a novel coronavirus disease (COVID-19) [1]. The disease is rapidly spread around the world causing thousands of deaths and posing critical challenges for public health and clinical research in the world. The outbreak was declared by the World Health Organization (WHO) as a public health emergency of international concern. Nowadays, there are more than 18 millions of confirmed cases of coronavirus across the world with a total of 702,903 deaths [2]. In Morocco, there are 28,500 confirmed cases and 345 deaths. Forecasts for the cumulative number of confirmed, recovered, active and death cases were recently provided [3]. To manage the pandemic spread several countries adopted proactive and preventive measures including home confinement of the population. However, there is evidence that these measures, particularly home confinement, can cause unprecedented disruption in the well-being of the population. Being forced to stay at home and the daily activities' restrictions could impact the citizens' health-related quality of life (HRQoL) and behavior-related lifestyle. It has been reported that the COVID-19 pandemic has an impact on psychological behaviors [4], mental health [5] and anxiety/depression [6]. The Moroccan population was under home confinement from March 20, 2020. Assessing rapidly and simply the HRQoL during crisis such as the home confinement is a challenge of interest to provide speedy information to authorities which allow best management of damages yielding in crisis situation. The EQ-5D instrument is a generic questionnaire developed by the Euroqol group for measuring the HRQoL by combining five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) [7]. The EQ-5D instrument is translated into more than 300 languages and exhibit good reliability and validity in both patients and general population. Herein, we used the EQ-5D-5L instrument to assess for the first time the impact of the home confinement on the HRQoL. Also, we evaluated the changes in behaviors by asking some questions related to lifestyle before and during the home confinement. These data can help the Moroccan authorities and other countries to more understand the impact of this crisis on citizens and therefore to set up adequate protocols for managing the post-confinement or possible future crisis. We provided two datasets: (1) data we collected before confinement from a sample of 484 individuals describing their HRQoL [8] and (2) data we collected during the home confinement period from a sample of 537 individuals describing their HRQoL and behavior-related lifestyle.