This study examined the contributions of mothers' social network stability and mother-infant behavioral synchrony on cortisol response in infants and their mothers during separation. The quality and stability of mothers' social network system and mother-infant bond have both been shown to affect infant neuroendocrine response. Yet, no studies have directly addressed how these two forms of social relationships might differentially affect infants' and mothers' neuroendocrine responses during separation. First-time mothers ( N = 133) and their 3-month-old infants participated in the study. Maternal social network stability, mother-infant behavioral synchrony, and mother and infant cortisol response during an infant challenge task were assessed. Behavioral synchrony accounted for significant variance in infants' cortisol response, and after adjusting for synchrony, mothers' network stability measures did not explain variance in infant cortisol. Social network stability, but not synchrony, accounted for significant variance in mothers' cortisol response. These results demonstrate that, when mothers and infants experience brief separation, the quality of their bond is associated with a lower stress response for infants; but for mothers, it is the longevity of her social relationships outside of the mother-infant relationship context that is associated with her lower stress response.