Background <p>Caring for patients with amyotrophic lateral sclerosis (ALS) involves demands that reduce caregivers' quality of life. Although caregiver burden and perceived social support was conceptualized as an independent correlate of quality of life rather than a factor operating primarily through caregiver burden. This study examined these associations within a stress-process framework in which perceived social support was conceptualized as an independent correlate rather than a buffering factor.</p> Methods <p>This cross-sectional analytical study included 118 informal caregivers of patients with ALS. Primary stressors were defined as patient functional status (ALSFRS-R), caregiving duration, and communication difficulty. Caregiver burden (Zarit Burden Interview) was considered a secondary stressor. Physical and mental quality of life were assessed using the SF-12, and perceived social support was measured with the Multidimensional Scale of Perceived Social Support. Hierarchical regression analyses were performed to examine associations specified in the conceptual model while controlling for caregiver sociodemographic and socioeconomic variables. Additional mediation analyses were conducted to examine whether caregiver burden mediated the relationship between perceived social support and quality of life.</p> Results <p>Poorer patient functional status was significantly associated with higher caregiver burden, whereas communication difficulty showed a positive but non-significant association after adjustment for caregiver characteristics. Caregiver burden showed negative associations with both physical and mental quality of life. Perceived social support remained positively associated with quality of life after adjustment for caregiver burden and contributed additional explained variance in the models. Mediation analyses showed no evidence that caregiver burden mediated the association between perceived social support and either physical or mental quality of life.</p> Conclusions <p>The findings are consistent with a stress-process framework in ALS caregiving, in which caregiver burden represents a central factor statistically associated with both caregiving stressors and quality of life, while perceived social support shows an independent association with quality of life. These findings suggest that both caregiver burden and perceived psychosocial resources may be relevant to caregiver well-being, although causal and intervention-related implications require further investigation.</p>