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Breast cancer challenges not only the patients who suffer from the disease but also their family caregivers. Little is known about how Iranian family caregivers are influenced.The objective of the study was to describe quality of life (QoL), well-being, sense of coherence (SOC), spirituality, and religious coping in family caregivers of patients with breast cancer at the time of diagnosis (T1) and 6 months after diagnosis (T2) and identify predictive factors of change in QoL.Data were collected from 150 family caregivers. The Persian version of Caregiver Quality of Life Index–Cancer, Sense of Coherence Scale, Spirituality Perspective Scale, Religious Coping Scale, and the Health Index were used at T1 and T2.The results showed significant increase in overall QoL (P = .00) and well-being (P = .03) at T2. However, ratings of their SOC (P = .03), spirituality (P = .01), and negative religious coping (P = .00) decreased. Multiple regression analyses revealed the rating of QoL at T1 as the strongest predictor in the rating of quality-of-life change at T2 followed by the degree of SOC, negative religious coping, and patients having more severe breast cancer (R2 = 0.64).Despite improved QoL in the sample from diagnosis to 6 months, family caregivers struggle to cope with the situation.It is suggested to develop and investigate the effects of support programs targeting coping ability in Iranian family caregivers to women with breast cancer.