Quality of life (QoL) is considered one of the measures of health outcomes. Limited research studies have assessed family caregivers’ QoL, especially among patients diagnosed with chronic disease. This study measures the QoL of caregivers who guardian patients diagnosed with cardiovascular disease, diabetes, cancer, and/or other diseases during the COVID-19 pandemic. Participants were primary caregivers who were supporting, in the last six months, individuals diagnosed with one of the previously mentioned chronic diseases. This included caregivers of patients admitted to a tertiary hospital from January 2021 to July of the same year (n = 1081); all participants completed the World Health Organization Quality of Life Assessment tool (WHOQOL-BREF) questionnaire. Caregivers of patients with cancer reported the highest mean level of QoL, followed by diabetes, cardiovascular diseases, then other different diseases (M = 3.80; M = 3.38; M = 3.37; and M = 2.51, respectively). A chi-square test of independence was performed to examine the relationship between the QoL of the four groups and their behaviors (i.e., caregivers’ psychological onuses and physical actions/reactions). The relation between these variables was significant, X2 (3, n = 1081) = 8.9, p = 0.001. The Kruskal–Wallis test indicated significant differences among the four groups (p ≤ 0.001). While the overall results of the QoL level of participants were low, a major recommendation of this study was to incorporate a QoL assessment to caregivers of chronically ill patients. Regular psychological and physical health check-ups of caregivers should be mandated in the healthcare system. Research studies should consider investigating and identifying the factors affecting health outcomes and positive developments which have a great impact on the wellbeing of both caregivers and patients on personal, organizational, and national levels.