Objective: To investigate quality of life (QoL) and QoL predictors among caregivers of individuals in first-episode psychosis (FEP). Methods: This longitudinal study investigated predictors of QoL in caregivers of 80 individuals in FEP over a 1-year follow-up period, measured using a single component extracted from the 36-item Short-Form Health Survey (SF-36). Results: Mediation analysis demonstrated that, at 1 year, high scores in the Self-Report Questionnaire (SRQ-20) were associated with high scores on the negative sub-scale of the Experience of Caregiving Inventory (ECI), which was also associated with low scores in the Essential Quality of Life (Essential QoL) component extracted from the SEF-36. Clinically, the resulting association indicates that depression and anxiety symptoms in caregivers at baseline are predictors of their 1-year quality of life, based on self-assessment of the caregiving experience. Conclusion: Supporting an individual in FEP can have a negative impact on QoL. Maintaining caregivers’ mental health and subjective evaluation of the caregiving experience must be primary goals of FEP services. Complementary studies of FEP caregivers’ QoL can support the design of personalized interventions in the near future.