question: INTRODUCTION: The outbreak of the COVID-19 has largely impacted individuals’ health and lifestyles. This study aimed to investigate people’s psychological well-being during the second phase of the COVID-19 pandemic. METHODS: We selected six indicators of psychological well-being: fear of COVID-19, loneliness, social interaction anxiety, generalized anxiety, PTSD, and depression. A sample of 231 Italian participants (56.3% women), with a mean age of 32.7 (SD=12.61), completed an online survey from February to March 2021, during the so called “second wave”. It included the Fear of COVID-19 Scale (FCV-19S), the UCLA Loneliness Scale- Version 3, the Generalized Anxiety Disorder 7-item Scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), the Impact of Event Scale–Revised (IES-R), and the Social Interaction Anxiety Scale (SIAS). RESULTS: Apart from loneliness, women reported lower levels of psychological well-being than men. Fairly good associations between all the detected variables were found. Based on a mediation model evaluation (in which generalized anxiety was introduced as a mediator in the relationship between fear of COVID-19, PTSD, loneliness, social interaction anxiety, and depression), except for social interaction anxiety, total and partial mediation effects suggested that generalized anxiety played a crucial role in exacerbating depressive symptoms during the pandemic. CONCLUSION: Our outcomes may expand the knowledge about the psychological well-being during the pandemic experience, with a focus on the mediating role of generalized anxiety.