The “empty-nest” elderly family has become increasingly prevalent among old people in China. This study aimed to explore the causality between empty nests and elders’ health using effective instrumental variables, including “whether old parents talk with their families when they are upset” and “ownership of housing”. The results showed that empty nests had a significantly adverse influence on elders’ physical health, cognitive ability and psychological health. Furthermore, urban elders’ cognitive ability was more influenced by empty nests than that of rural elders. Additionally, the effects of an empty nest on elders” health were more significant among female, single elders and senior rural elders. “Living resources”, “availability of medical treatment” and “social activity engagement” were found to be significant mediators between empty nests and elders’ health, accounting for 35% of the total effect.