Identified in China at the end of 2019, the COVID-19 infection has increased exponentially worldwide. Together with the threat of physical illness, this pandemic brought negative impacts on mental health. Additionally, the pandemic also interfered with other life domains: closings of schools and companies, restricted access to public places, changes in work and home routines and increased uncertainty due to the economic repercussions. This study examines people's experiences and mental health in the 6th consecutive lockdown week in Portugal and compares with the pre-confinement population's mental health. Specifically, we explore the difficulties experienced by the general population while in lockdown, their strategies to cope with it, and its impact on mental health. One thousand five hundred and two participants undergoing the 6th lockdown week answered a web-based cross-sectional survey. Demographic information, living conditions, confinement-related difficulties or challenges, strategies to cope with lockdown and mental health dimensions were assessed. Some difficult confined related experiences and sociodemographic variables were associated with poor mental health. When compared to our findings, the general population' mental health was better before the pandemic. Lockdown challenges experienced by participants and their strategies to cope with confinement predicted 10 to 42% of the variance in mental health dimensions. This study identified several mental health-protective and risk factors related to long-term compulsory confinement. Individual strategies to prevent mental health problems are discussed. Additionally, our findings may inform national health agencies and governments on measures to enhance mental health among the quarantined general population.