This study aims to investigate the serial multiple mediation of physical activity and perceived stress in the relationship between individual social capital and quality of life (QOL) in breast cancer survivors (BCSs). This study was conducted among 520 BCSs between March and April 2017 in Shanghai, China. Data were collected using the Individual Social Capital Scale, the Health-Promoting Lifestyle Profile-II, the Perceived Stress Scale-14 and the EORTC QLQ-C30. Ordinary least-squares regression and the bootstrap method was used to test the significance of the serial multiple mediation model. The serial-multiple mediations of physical activity and perceived stress were found significant in the relationship of QOL with all five dimensions of individual social capital. The separate mediations of two single mediating variables were found significant in the relationship of QOL with control over life and feeling about the community. In the relationship of QOL with social participation, social network and social support, the separate mediation of physical activity was significant, while the separate mediation of perceived stress was not significant. A multidisciplinary team approach and a variety of delivery systems are needed to address the social, physical and psychological issues for improving QOL among BCSs.