Due to COVID-19, the workload experienced by caregivers has increased markedly which has led them to experience fatigue, anxiety and depression. This study aims to determine the relationship between quality of life and depression in caregivers of post-COVID-19 patients in two regions of Peru. In a cross-sectional analytical study, the sample was non-probabilistic and by snowball, and consisted of 730 caregivers, to whom the questionnaires “Modified Betty Ferell Quality of Life” and the “Beck Depression Inventory” were applied. It was determined that being a male caregiver (OR: 2.119; 95% CI: 1.332–3.369) was associated with a good quality of life. On the other hand, caregivers who had children (OR: 0.391; 95% CI: 0.227–0.675), were vaccinated against COVID-19 (OR: 0.432; 95% CI: 0.250–0.744), were immediate family members (OR: 0.298; 95% CI: 0.117–0.761) and had high depression (OR: 0.189; 95% CI: 0.073–0.490) were associated with poor quality of life. The results of this study allow us to conclude the association between depression and poor quality of life in caregivers of these patients so it is necessary to monitor the mental health of caregivers, and to develop adaptation strategies to pandemic conditions.