BACKGROUND: Interoception - the processing of the internal state of the body - has been consistently tied to well-being and mental health, which in turn have been severely challenged by the COVID-19 pandemic. Moreover, the fact that symptoms of COVID-19 (high temperature, shortness of breath, fatigue, and even gastro-intestinal problems) directly alter interoceptive signals has fueled people\'s tendency to constantly check their internal bodily state. OBJECTIVES: In this longitudinal study we tested for changes in interoception and psychophysiological health and well-being during different stages of the pandemic in 2020 and assessed their potential association. To highlight this association, we combined both subjective (i.e., self-reported questionnaires) and objective (i.e., measures of heart rate variability, HRV and of interoceptive accuracy) measures. METHODS: 245 Italian participants who had completed the Multidimensional Assessment of Interoceptive Awareness (MAIA-2) prior to the onset of the pandemic, repeated the questionnaire during the first national lockdown in Italy, and four months after restrictions. Participants also completed survey measures of depression (PHQ-9), anxiety (STAI), and sleep disturbance (PSQI). A sub-sample of 28 participants, who had completed the heartbeat counting task (HCT) and a measure of heart rate variability (HRV), was tested again remotely, in the same time windows, using phone applications and photoplethysmography. RESULTS: While performance in the HCT remained unvaried, MAIA-2 scores consistently increased from before the pandemic to the national lockdown, and remained largely unvaried after four months. The national lockdown was associated with the lowest psychophysiological health and well-being, as evidenced by a decrease in HRV compared to before the pandemic and by higher scores in self-reported depression, anxiety, and sleep disturbance compared to four months after the lockdown. Interestingly, psychophysiological health and well-being were predicted by specific regulatory components of interoception (e.g., the ability to regulate distress by focusing on body sensations and experiencing one\'s body as safe and trustworthy). CONCLUSIONS: Our results suggest an increased attention towards visceral signals during the COVID-19 pandemic, and highlight the positive role of specific components of interoception in contributing to well-being, suggesting that novel interventions aimed at increasing interoception may be developed to protect against stressful life events such as COVID-19.