The imposition of lockdowns during the COVID-19 pandemic placed individuals under conditions of environmental stress, threatening individual and collective wellbeing. This study aimed to investigate the temporal effects of isolation and confinement during and after the Italian lockdown on decision-making, risk propensity, and cognitive control processes. The present study covered almost the entire Italian lockdown period (each week from the end of March to mid-May 2020), plus a follow-up measure (September 2020). At each time-point, respondents completed online behavioral tasks, which involved measuring risk-propensity (Balloon Analogue Risk Task), decision-making (Iowa Gambling Task), and cognitive flexibility (Category Switch Task). They also filled in questionnaires regarding subjective stress and anxiety. The main findings showed that the decision-making abilities of the respondents were affected as the confinement progressed. Furthermore, individuals who were more subjectively impacted by the lockdown/isolation experience exhibited impaired decision-making, especially during the lockdown. The results of the study highlight that prolonged confinement may affect human decision making, and help understand individuals’ misbehaviors during emergencies and develop effective countermeasures aimed at reducing the burden of the healthcare system.