<p><b>Introduction.</b> This study aims to investigate the effect of loneliness as a psychological vulnerability on health-related quality of life (HRQoL) and to test some explanatory mechanisms for a better understanding of how loneliness leads to a decrease in the mental and physical health components of HRQoL among older adults. We tested the mediating effect of gratitude and the moderating effect of interpersonal sensitivity, firstly in the relationship between loneliness and mental health and secondly, in the relationship between loneliness and physical health. <b>Method.</b> The sample consisted of 441participants (164 male; 277 female) aged 65 to 90 years old. A structural equation model was tested using IBM SPSS Amos v.26. <b>Results.</b> Gratitude significantly mediated only the relationship between loneliness and the mental health component of HRQoL. Both loneliness and interpersonal sensitivity negatively predicted the two components of HRQoL. Interpersonal sensitivity significantly moderated the relationship between loneliness and the mental and physical health components. <b>Conclusions.</b> Loneliness had a stronger negative impact on mental health, but our findings suggest that the effect on physical health was also significant. Loneliness in itself decreased mental health, but its effect was stronger in older adults with higher interpersonal sensitivity. On the other hand, the impact of loneliness on physical health was significant only when interpersonal sensitivity was low or medium. Our results highlighted some insights into the factors that contribute to a decline in HRQoL in the third age.</p>