Background: This study investigated the associations of maternal oxytocin, self-reported attachment insecurity and depressive symptoms with maternal caregiving sensitivity at 3–4 months postpartum, observed during the ‘free play’ and ‘reunion’ episodes of the Still Face Procedure. Methods: 112 mothers completed questionnaires and gave blood samples to determine oxytocin plasma levels before (time 1) and after participating in the Still Face Procedure with their infant (time 2). Results: Sensitive maternal caregiving during the free play episode was predicted by ‘good’ infant behavior; during the reunion episode it was predicted by ‘good’ infant behavior, higher baseline levels of maternal oxytocin and a greater maternal oxytocin response, or in other words, a larger increase in maternal oxytocin level from time 1 to time 2. With other variables free to vary, baseline maternal oxytocin levels mediated an inverse relation between maternal adult attachment avoidance and sensitive maternal caregiving during the reunion episode. Conclusion: Results highlight the association between oxytocin and sensitive maternal caregiving and suggest that oxytocin is a biological mechanism through which maternal attachment insecurity affects early parenting quality.