Background Anxiety disorders are common in youth and cause significant distress and impairment to the individual and family. Oxytocin (OT), a nine amino acid peptide, is implicated in anxiety regulation and modulation of close interpersonal and attachment behavior. Anxiety disorders have been linked to low levels of salivary OT in youth. Research has also linked oxytocinergic functioning to social support, warm contact, and bonding, and indicated that contact with attachment figures stimulates OT response. We examined OT response to a brief, positive youth–mother interaction in clinically anxious youth. We investigated whether quality of the youth–mother interaction as well as the presence of particular anxiety disorders, are associated with youth OT response. Method Salivary OT from 41 youth with primary DSM‐5 anxiety disorders was assayed before and after a 7‐min youth–mother interaction that was later systematically coded by two reliable coders. Youth and mothers also completed rating scales of youth anxiety symptoms. Results Affective touch, maternal sensitivity, maternal intrusiveness, youth engagement, and youth initiative all contributed significantly to predicting youth OT response. Repeated measures analyses showed that when affective touch was high youth had greater OT response. OT response was positively associated with the presence of separation anxiety disorder (SAD) and with child ratings of separation anxiety. Conclusions The findings highlight the importance of maternal and dyadic behavior patterns to oxytocinergic response in clinically anxious youth, shed light on the association between OT and SAD, and point to possible intervention strategies.