Introduction Mental illness such as schizophrenia is a major public health concern. In France, the economic cost of schizophrenia represents 2% of total medical expenditures. Schizophrenia has an impact on health and quality of life not only for patients but also for relatives. Family psychoeducation is a complementary therapeutic intervention to ordinary clinical care deigned to alleviate the burden of care among relatives of patients with schizophrenia. Literature suggests such programs including the patients’ family members reduce the risk of relapse. Current studies also suggest that negative emotions expressed by family members have negative consequences on patients’ mental health and need to be addressed. However, family psychoeducation is still underdeveloped in France. The objective of this study was to assess the longitudinal outcome on depression level of a psychoeducation program for relatives of schizophrenic patients. The program was held in Paris and Région Île-de-France “Cluster ProFramille Île-de-France” between 2012 and 2014. Methods Level of participant's depression was assessed by the Center for Epidemiologic Studies – Depression Scale (CES-D). Measures of depression were made for four time points: 2 months before joining the program (T1), at the beginning of the program (T2), at midpoint of the first program module (3 months, T3) and at the end of the first program module (6 months, T4). Repeated-measures ANOVA were performed to assess longitudinal change in a participant's level of depression. Type of coping strategies, knowledge about the disease, dominant thoughts and emotional progress are assessed by the program. Univariate correlation with CES-D differences between T1 and T4 were assessed. Variables with a significant association were included in a multivariate linear model to explain CES-D difference. Results Sixty-five relatives participated to the “Cluster ProFramille Île-de-France” between 2012 and 2014 and terminated with the first module of the program. Repeated-measures ANOVA on CES-D scores between T1 and T4 (8 months) showed a significant decrease in average scores for all participants. The mean of decrease was 7 points, equivalent to a 26.6% pre-post decrease level of depression. Significant univariate correlations with depression decrease over 8 months were with “psychomotor tiredness”, “frequent worries” and “dealing with worries”. Multivariate linear regression only confirmed the significant role of diminishing fatigue in relation to the decrease of depression. Conclusion Our study's results showed that the ProFamille program was efficient in reducing the level of depression for its participants over an 8 month period. As the participants progressed on managing their fatigue, their depressed moods improved.