Purpose: The purpose of this study was to evaluate the reliability and validity of the Caregivers Quality of Life Cancer index scale (CQoLC) in a sample of spouses of French cancer patients. Methods: The CQoLC, the Medical Outcomes Study Short Form 12 (MOS SF-12) and the State-Trait Anxiety Inventory (STAI) were administered to 300 spouses aged 21–85 years. Clinical data such as severity of cancer, medical treatment and duration of illness were obtained from a review of medical records. Results: An exploratory factor analysis yielded a 23-item measure with one factor explaining 38.76% of the variance: labeled impairment of quality of life. The correlations between this factor and MOS SF-12 were negative for the physical component (ρ = −0.351, p < 0.001) and positive for the mental component (ρ = 0.184, p < 0.005). One-way ANOVA with STAI scores indicated good discriminant validity (F[2, 237] = 4.80, p < 0.01, η2 = 0.04). Participants with low anxiety had a better quality of life than those with moderate and high anxiety. Conclusions: The findings indicate that the CQoLC has sufficient validity and reliability to assess the impairment of quality of life in spouses of French cancer patients.